Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact

Review 10.1172/JCI143780

Overcoming innate immune barriers that impede AAV gene therapy vectors

Manish Muhuri,1,2,3 Yukiko Maeda,1,3,4 Hong Ma,1 Sanjay Ram,5 Katherine A. Fitzgerald,6 Phillip W.L. Tai,1,2,3 and Guangping Gao1,2,7

1Horae Gene Therapy Center,

2Department of Microbiology and Physiological Systems,

3VIDE Program,

4Department of Medicine,

5Division of Infectious Diseases and Immunology,

6Program in Innate Immunity, Department of Medicine, and

7Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Address correspondence to: Guangping Gao or Phillip W.L. Tai, Horae Gene Therapy Center, University of Massachusetts Medical School, 386 Plantation Street, Worcester, Massachusetts 01605, USA. Phone: 508.856.3394; Email: guangping.gao@umassmed.edu (GG). Phone: 774.455.4559; Email: Phillip.Tai2@umassmed.edu (PWLT).

Authorship note: MM and YM contributed equally to this work.

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

1Horae Gene Therapy Center,

2Department of Microbiology and Physiological Systems,

3VIDE Program,

4Department of Medicine,

5Division of Infectious Diseases and Immunology,

6Program in Innate Immunity, Department of Medicine, and

7Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Address correspondence to: Guangping Gao or Phillip W.L. Tai, Horae Gene Therapy Center, University of Massachusetts Medical School, 386 Plantation Street, Worcester, Massachusetts 01605, USA. Phone: 508.856.3394; Email: guangping.gao@umassmed.edu (GG). Phone: 774.455.4559; Email: Phillip.Tai2@umassmed.edu (PWLT).

Authorship note: MM and YM contributed equally to this work.

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

1Horae Gene Therapy Center,

2Department of Microbiology and Physiological Systems,

3VIDE Program,

4Department of Medicine,

5Division of Infectious Diseases and Immunology,

6Program in Innate Immunity, Department of Medicine, and

7Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Address correspondence to: Guangping Gao or Phillip W.L. Tai, Horae Gene Therapy Center, University of Massachusetts Medical School, 386 Plantation Street, Worcester, Massachusetts 01605, USA. Phone: 508.856.3394; Email: guangping.gao@umassmed.edu (GG). Phone: 774.455.4559; Email: Phillip.Tai2@umassmed.edu (PWLT).

Authorship note: MM and YM contributed equally to this work.

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

1Horae Gene Therapy Center,

2Department of Microbiology and Physiological Systems,

3VIDE Program,

4Department of Medicine,

5Division of Infectious Diseases and Immunology,

6Program in Innate Immunity, Department of Medicine, and

7Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Address correspondence to: Guangping Gao or Phillip W.L. Tai, Horae Gene Therapy Center, University of Massachusetts Medical School, 386 Plantation Street, Worcester, Massachusetts 01605, USA. Phone: 508.856.3394; Email: guangping.gao@umassmed.edu (GG). Phone: 774.455.4559; Email: Phillip.Tai2@umassmed.edu (PWLT).

Authorship note: MM and YM contributed equally to this work.

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

1Horae Gene Therapy Center,

2Department of Microbiology and Physiological Systems,

3VIDE Program,

4Department of Medicine,

5Division of Infectious Diseases and Immunology,

6Program in Innate Immunity, Department of Medicine, and

7Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Address correspondence to: Guangping Gao or Phillip W.L. Tai, Horae Gene Therapy Center, University of Massachusetts Medical School, 386 Plantation Street, Worcester, Massachusetts 01605, USA. Phone: 508.856.3394; Email: guangping.gao@umassmed.edu (GG). Phone: 774.455.4559; Email: Phillip.Tai2@umassmed.edu (PWLT).

Authorship note: MM and YM contributed equally to this work.

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

1Horae Gene Therapy Center,

2Department of Microbiology and Physiological Systems,

3VIDE Program,

4Department of Medicine,

5Division of Infectious Diseases and Immunology,

6Program in Innate Immunity, Department of Medicine, and

7Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Address correspondence to: Guangping Gao or Phillip W.L. Tai, Horae Gene Therapy Center, University of Massachusetts Medical School, 386 Plantation Street, Worcester, Massachusetts 01605, USA. Phone: 508.856.3394; Email: guangping.gao@umassmed.edu (GG). Phone: 774.455.4559; Email: Phillip.Tai2@umassmed.edu (PWLT).

Authorship note: MM and YM contributed equally to this work.

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

1Horae Gene Therapy Center,

2Department of Microbiology and Physiological Systems,

3VIDE Program,

4Department of Medicine,

5Division of Infectious Diseases and Immunology,

6Program in Innate Immunity, Department of Medicine, and

7Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Address correspondence to: Guangping Gao or Phillip W.L. Tai, Horae Gene Therapy Center, University of Massachusetts Medical School, 386 Plantation Street, Worcester, Massachusetts 01605, USA. Phone: 508.856.3394; Email: guangping.gao@umassmed.edu (GG). Phone: 774.455.4559; Email: Phillip.Tai2@umassmed.edu (PWLT).

Authorship note: MM and YM contributed equally to this work.

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

Published January 4, 2021 - More info

Published in Volume 131, Issue 1 on January 4, 2021
J Clin Invest. 2021;131(1):e143780. https://doi.org/10.1172/JCI143780.
© 2021 American Society for Clinical Investigation
Published January 4, 2021 - Version history
View PDF

The field of gene therapy has made considerable progress over the past several years. Adeno-associated virus (AAV) vectors have emerged as promising and attractive tools for in vivo gene therapy. Despite the recent clinical successes achieved with recombinant AAVs (rAAVs) for therapeutics, host immune responses against the vector and transgene product have been observed in numerous preclinical and clinical studies. These outcomes have hampered the advancement of AAV gene therapies, preventing them from becoming fully viable and safe medicines. The human immune system is multidimensional and complex. Both the innate and adaptive arms of the immune system seem to play a concerted role in the response against rAAVs. While most efforts have been focused on the role of adaptive immunity and developing ways to overcome it, the innate immune system has also been found to have a critical function. Innate immunity not only mediates the initial response to the vector, but also primes the adaptive immune system to launch a more deleterious attack against the foreign vector. This Review highlights what is known about innate immune responses against rAAVs and discusses potential strategies to circumvent these pathways.

Preview pages

Reset
Next Page 0 Back

Continue reading with a subscription.

A subscription is required for you to read this article in full. If you are a subscriber, you may sign in to continue reading.

Already subscribed?

Click here to sign into your account.

Don't have a subscription?

Please select one of the subscription options, which includes a low-cost option just for this article.

At an institution or library?

If you are at an institution or library and believe you should have access, please check with your librarian or administrator (more information).

Problems?

Please try these troubleshooting tips.

  • Purchase this article
  • $10
  • Purchasing this article will give you full access for the calendar year.
  • Purchase article
  • Purchase Site Pass
  • $25
  • This will give you access to every article on the site for 24 hours.
  • Order site pass
  • Online subscription
  • $95
  • Individual online subscriptions give you full online access for the calendar year.
  • Individual online subscriptions ordered from September 1st on will receive access for the remainder of current year as well as for the full following year subscription term.
  • Order Online
  • JCI This Month subscription
  • $135
  • JCI This Month is a 16- to 20-page overview of the articles published each month
  • Subscribing to JCI This Month also gives subscribers full online access for the calendar year.
  • *Price outside U.S. and Canada: $195.
  • JCI This Month + Online
Advertisement
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts