Many gene therapy strategies designed to deliver a normal copy of a gene to cells carrying a disease-causing genetic mutation rely on a modified virus to transfer the gene product into affected tissues. One technology platform that is well suited for in vivo delivery of genes is based on adeno-associated viruses (AAV). As these novel therapies move closer to commercialization, so do the methods for large-scale production and efficient delivery of AAV vectors.
A collection of papers explores the progress and challenges in refining the production and use of AAV-based vectors. Allay et al. describe a large-scale, commercially relevant method for producing and purifying an AAV vector for use in a clinical study. In another article, Montenegro-Miranda et al. show that an immunosuppressive drug used in conjunction with gene therapy to treat an inherited liver disorder impaired the activity of certain types of AAV gene delivery vectors but not others. Yuan and coworkers present an improved and simplified method for generating producer cell lines that yield large amounts of AAV and exhibit stable growth in another article.
Lu et al. developed a strategy for minimizing the unwanted production of AAV capsid protein by contaminating replication-competent virus that can provoke an immune response. In yet another article, Ma and colleagues have further optimized their method for delivering a mixed population of AAV2 vectors to enable high-efficiency transfer of large genes.
Finally, a provocative commentary by J. Fraser Wright, explores how the design, manufacture, and characterization of gene therapy products have evolved based on the experience gained and lessons learned from first-generation clinical studies.
“Clinical proof of concept of AAV gene therapy has been realized in several diseases. The focus is now on issues related to commercialization including methods for large scale and high quality production of vectors," says James M. Wilson, MD, PhD, Editor-in-Chief, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Illustration: Microsoft clipart.
Human Gene Therapy News Release (05/18/11)
Medical News Today (05/19/11)
Abstract (Human Gene Therapy; 22(5), 595-604 (05/11))
Abstract (Human Gene Therapy; 22(5), 605-612 (05/11))
Abstract (Human Gene Therapy; 22(5), 613-624 (05/11))
Abstract (Human Gene Therapy; 22(5), 625-632 (05/11))
Abstract (Human Gene Therapy; 22(5), 633-640 (05/11))
Commentary (Human Gene Therapy; 22(5), 519-521 (05/11))