The Gene Therapy Program is at the forefront of the science and translation of adeno-associated virus (AAV) vectors for the development of human and animal therapeutics.
This program represents our ambitious commitment to developing cutting-edge vector technologies. Despite tremendous progress in AAV research in the last 25 years and its continued clinical success, there is a significant opportunity to improve the performance of the AAV platform for gene therapy and to successfully apply it to a broader range of therapeutic applications.
Our diversified approach focuses on delivering advanced vectors for traditional gene therapy applications as well as vectors tailored specifically for genome editing. The design of these next-generation AAV vectors is guided by experimental results from studies on the basic biology of AAV that leverage our world-class resources in molecular, structural, cell, and computational biology.
Since the discovery of AAVs in the 1960s, AAV-based vectors have become the platform of choice for in vivo gene therapy. AAV was originally identified as a contaminant of laboratory preparations of adenoviruses, and the first AAV vectors were created from AAV serotype 2 (AAV2). Although the safety profile of AAV2 was an improvement over other viral and non-viral vectors, its use was limited to certain cell types of the retina. From this early work, an AAV2-based gene therapy was developed to treat patients with a rare form of inherited blindness, which has since become the first FDA approved gene therapy.
In the mid-1990s, the Wilson Laboratory sought to improve the performance of AAVs by developing vectors based on other known serotypes. This early development effort, referred to as AAV 1.0, produced vectors with improved transduction in skeletal and cardiac muscle. For example, AAV1 formed the basis of a novel therapeutic developed for the treatment of an inherited form of high triglycerides by UniQure, which became the first gene therapy approved in Europe. An AAV5-based vector with improved transduction profiles was also developed at the National Institutes of Health (NIH) during this time.
In work that began in 2000, a large and diverse family of endogenous AAVs were identified from natural sources and used to develop improved vectors. This new technology platform, AAV 2.0, was widely and freely distributed to the academic community. Subsequent licensing and sublicensing to multiple biotech companies has led to the development of 28 product candidates, and has accounted for approximately 70% of all AAV gene therapy clinical trials from 2012 through 2014.
A number of academic and commercial laboratories have attempted to improve the performance of AAV vectors since the creation of the AAV 2.0 platform, however, it is difficult to assess whether these incremental efforts have yielded substantial improvements in efficiency and safety over the original AAV 2.0 vectors, since very little research has been done with these new vectors in large animals or humans. In the case of biopharmaceutical efforts, insufficient information is disclosed to allow for an independent confirmation of relative performance.
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