Analytical methods for preclinical stage gene therapy programs

Using a process confirmation vector, researchers developed and optimized a size exclusion chromatography (SEC) with UV and multi-angle light scattering (MALS) method to measure the level of empty capsids during manufacturing. In a new study, the researchers showed that SEC-MALS outperformed other analytical methods and correlated well with sedimentation velocity analytical ultracentrifugation (SV-AUC) values of full-to-empty particles. The study is published in the peer-reviewed journal Human Gene Therapy. Click here to read the article now.

Analytical capabilities must be able to quantify the levels of empty and full capsids in manufactured adeno-associated viruses (AAV) during preclinical stage gene therapy development.

Bryan Troxell, from StrideBio, and coauthors, showed that SEC-MALS was linear, accurate, and precise while achieving chromatography quality control recommendations. Furthermore, compared to other stability-indicating assays, SEC-MALS performed similarly to droplet digital PCR, capsid enzyme-linked immunosorbent assay, and infectivity assays in accelerated stress studies.

“The data supports that SEC-MALS is a robust analytical technique for advancement of gene therapy programs,” state the investigators.

“It has become increasingly clear that empty vector capsids represent undesirable contaminants in preclinical and clinical-grade AAV gene therapy products,” says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Chan Medical School. “The ability to precisely measure the level of these contaminants is an important step for improving the quality and consistency of these products.”

About the Journal
Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy and eight other international gene therapy societies, was the first peer-reviewed journal in the field and provides all-inclusive access to the critical pillars of human gene therapy: research, methods, and clinical applications. The Journal is led by Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Chan Medical School, and an esteemed international editorial board. Human Gene Therapy is available in print and online. Complete tables of contents and a sample issue are available on the Human Gene Therapy website.

About the Publisher
Mary Ann Liebert, Inc. is a global media company dedicated to creating, curating, and delivering impactful peer-reviewed research and authoritative content services to advance the fields of biotechnology and the life sciences, specialized clinical medicine, and public health and policy. For complete information, please visit the Mary Ann Liebert, Inc. website.