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ResearchIn-Press PreviewCell biologyOncology Open Access | 10.1172/JCI195639

Discovery and therapeutic delivery of microRNAs targeting deregulated glioblastoma pathways inhibits tumor growth in mice

Shekhar Saha,1 Ying Zhang,1 Myron K. Gibert Jr.,1 Collin Dube,1 Farina Hanif,1 Elizabeth Qian Xu Mulcahy,1 Sylwia Bednarek,1 Yunan Sun,1 Pawel Marcinkiewicz,1 Xiantao Wang,2 Gijung Kwak,3 Ahsan H. Polash,2 Haolin Li,3 Kadie Hudson,1 Manikarna Dinda,4 Tapas Saha,5 Matthew McCord,6 Fadila Guessous,4 Nichola Cruickshanks,4 Rossymar Rivera Colon,4 Lily Dell'Olio,4 Rajitha Anbu,4 Wenjie Liu,4 Songy Choi,4 Benjamin Kefas,4 Pankaj Kumar,7 Alexander L. Klibanov,8 David Schiff,9 Jung Soo Suk,3 Justin Hanes,10 Jamie Mata,11 Markus Hafner,2 and Roger Abounader4

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Saha, S. in: PubMed | Google Scholar |

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Zhang, Y. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Gibert Jr., M. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Dube, C. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Hanif, F. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Mulcahy, E. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Bednarek, S. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Sun, Y. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Marcinkiewicz, P. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Wang, X. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Kwak, G. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Polash, A. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Li, H. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Hudson, K. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Dinda, M. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Saha, T. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by McCord, M. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

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1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Cruickshanks, N. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Rivera Colon, R. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Dell'Olio, L. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Anbu, R. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Liu, W. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Choi, S. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Kefas, B. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Kumar, P. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Klibanov, A. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

Find articles by Schiff, D. in: PubMed | Google Scholar

1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

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1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

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1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

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1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

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1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States of America

2National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States of America

3Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, United States of America

4Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States of America

5Swiss Re, Healthcare, Bengaluru, India

6Department of Pathology, University of Virginia School of Medicine, Charlottesville, United States of America

7Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, United States of America

8Cardiovascular Division, University of Virginia, Charlottesville, United States of America

9Neurology, University of Virginia Health System, Charlottesville, United States of America

10Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States of America

11Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, United States of America

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Published June 30, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI195639.
Copyright © 2026, Saha et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 30, 2026 - Version history
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Abstract

Glioblastoma is a fatal primary malignant brain tumor, with an average survival of 15 months despite surgical resection, chemotherapy, and radiation therapy. Due to the concurrent deregulation of numerous genes in glioblastoma, molecular monotherapies have not improved clinical outcomes. Evidence suggests that targeting multiple deregulated molecules is essential for better therapies; however, this is limited by the lack of suitable drugs and increased toxicity of combination therapies. To address this, we hypothesized that miRNAs, small gene-regulatory RNAs that suppress mRNA, could simultaneously inhibit multiple deregulated genes in glioblastoma, and be used for more effective therapies. We identified regulatory miRNAs — those that target several deregulated genes in glioblastoma — using a combination of PAR-CLIP screening, TCGA data analyses and an algorithm to rank target importance and miRNA therapeutic potential. We selected two tumor suppressor miRNAs, miR-340 and miR-382, and one oncogenic miRNA, miR-17 and showed that they target critical glioblastoma pathways and alter cell growth, survival, invasion, and in vivo tumor growth. We developed and successfully applied a miRNA therapeutic delivery approach using Brain Penetrating Nanoparticles combined with MRI-guided focused ultrasound and microbubbles, to inhibit established tumor growth and to extend animal survival. This strategy offers a promising approach for translating miRNA-based therapies into clinical trials for glioblastoma and other cancers.

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