Recombinant adeno-associated virus vectors in the treatment of rare diseases

Abstract

Introduction: An estimated 25 million Americans are living with rare diseases. Adeno-associated virus (AAV)-mediated gene therapy is an emerging therapeutic option for > 7000 identified rare diseases. This paper highlights the benefits of AAV therapy compared to conventional small molecules, discusses current pre-clinical and clinical applications of AAV-mediated gene therapy, and offers insights into cutting edge research that will shape the future of AAV for broad therapeutic use.

Areas covered: In this review the biology of AAV and our ability to generate disease-specific variants is summarized. Limitations of current therapy are reviewed, with an emphasis on immune detection of virus, viral tropism and tissue targeting, and limitations of gene expression. Information for this review was found using PubMed and clinicaltrials.gov.

Expert opinion: Currently the scope of clinical trials of AAV gene therapy is concentrated in an array of Phase I/II safety trials with less than two dozen rare diseases featured. Pre-clinical, translational studies are expanding in number as developments within the last decade have made generation of improved AAV vectors available to more researchers. Further, one bottleneck that is being overcome is the availability of disease models, which will allow for improved preclinical testing and advancement of AAV to more clinical applications.

Keywords:

• adeno-associated virus
• adeno-associated virus vectors
• gene therapy
• orphan disease
• rare disease

Declaration of interest

We would like to acknowledge funding support to RJ Samulski from University of Pennsylvania ODC (MPSI-13-010-01) and NIH (R01 AI080726, R01 DK084033, P01 HL112761, R01 AI072176, R01 AR064369). RJ Samulski holds patents related to AAV vector technology and is a founder of companies that are developing commercial applications for AAV gene therapy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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