Product-Related Impurities in Clinical-Grade Recombinant AAV Vectors: Characterization and Risk Assessment
Open Access
- 2 March 2014
- journal article
- review article
- Published by MDPI AG in Biomedicines
- Vol. 2 (1), 80-97
- https://doi.org/10.3390/biomedicines2010080
Abstract
Adeno-associated virus (AAV)-based vectors expressing therapeutic genes continue to demonstrate great promise for the treatment of a wide variety of diseases and together with other gene transfer vectors represent an emerging new therapeutic paradigm comparable in potential impact on human health to that achieved by recombinant proteins and vaccines. A challenge for the current pipeline of AAV-based investigational products as they advance through clinical development is the identification, characterization and lot-to-lot control of the process- and product-related impurities present in even highly purified preparations. Especially challenging are AAV vector product-related impurities that closely resemble the vector itself and are, in some cases, without clear precedent in established biotherapeutic products. The determination of acceptable levels of these impurities in vectors prepared for human clinical product development, with the goal of new product licensure, requires careful risk and feasibility assessment. This review focuses primarily on the AAV product-related impurities that have been described in vectors prepared for clinical development.Keywords
This publication has 61 references indexed in Scilit:
- Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia BNew England Journal of Medicine, 2011
- Systemic Elimination ofde novoCapsid Protein Synthesis from Replication-Competent AAV Contamination in the LiverHuman Gene Therapy, 2011
- Good Manufacturing Practice Production of Self-Complementary Serotype 8 Adeno-Associated Viral Vector for a Hemophilia B Clinical TrialHuman Gene Therapy, 2011
- A viral assembly factor promotes AAV2 capsid formation in the nucleolusProceedings of the National Academy of Sciences, 2010
- Gene Therapy for Leber's Congenital Amaurosis is Safe and Effective Through 1.5 Years After Vector AdministrationMolecular Therapy, 2010
- Undetectable Transcription of cap in a Clinical AAV Vector: Implications for Preformed Capsid in Immune ResponsesMolecular Therapy, 2009
- Treatment of Leber Congenital Amaurosis Due toRPE65Mutations by Ocular Subretinal Injection of Adeno-Associated Virus Gene Vector: Short-Term Results of a Phase I TrialHuman Gene Therapy, 2008
- Safety and Efficacy of Gene Transfer for Leber's Congenital AmaurosisNew England Journal of Medicine, 2008
- Effect of Gene Therapy on Visual Function in Leber's Congenital AmaurosisNew England Journal of Medicine, 2008
- Recombinant adeno-associated virus purification using novel methods improves infectious titer and yieldGene Therapy, 1999