The potential for gene therapy to effectively treat HIV, cancer, and various other maladies holds immense promise. Despite advancements in this field, the cost of this treatment remains prohibitively high- thereby restricting access to patients and research institutions alike. The Adair lab has extensive experience manufacturing gene modified blood cells for various gene therapy applications. Previously, we have re-engineered technology for automated blood cell separation to make gene therapy a cost-effective, portable application within reach of healthcare providers throughout the world who lack state-of-the-art cGMP laboratory infrastructure. This technology could permit ex vivo gene transfer into multiple cell types for a variety of gene therapy applications. However, for some diseases such as Fanconi Anemia (FA), ex vivo gene therapy may not be the most appropriate approach. Here, the Adair lab is examining whether in vivo gene delivery is a viable treatment option.
Pharmaceutical drug manufacturing must abide by Current Good Manufacturing Practice (cGMP) guidelines which often necessitate a facility with high tech laboratory equipment and millions of dollars in investment. Recent innovations in biotechnological hardware however have made it possible to isolate and culture cells within an automated closed system that abides by cGMP guidelines. This type of a machine occupies the space of an ordinary countertop, thus making it highly desirable for portable, point-of-care applications that would dramatically expand access to curative gene therapies. The Adair lab is developing this technology at Fred Hutch, with the hope that these advancements will be utilized in clinical settings in the near future.
The Adair lab is also looking at in-vivo gene therapy as a treatment method that can be broadly scaled while simultaneously improving efficacy for disease targets wherein genetically modified cells have a selective advantage over non-modified cells. For these diseases, intravenous administration of non-viral machinery to deliver therapeutic genetic changes allows cells to be genetically modified within their native environments. This overcomes the limitations of ex vivo gene therapy such as the loss of stem cell multipotency and engraftment potential. Two possible approaches for in vivo delivery include (1) non-pathogenic viruses for delivery of large transgene cassettes, or (2) non-viral delivery of gene editing machinery to create precise genomic alterations of therapeutic value. Although significant steps must be taken before in-vivo gene therapy can safely be applied to humans, the potential for it to improve treatment while vastly reducing costs would represent a major milestone in modern medicine.