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Review
. 2014 Mar 3;2(1):80-97.
doi: 10.3390/biomedicines2010080.

Product-Related Impurities in Clinical-Grade Recombinant AAV Vectors: Characterization and Risk Assessment

J Fraser Wright  1   2
Affiliations
Review

Product-Related Impurities in Clinical-Grade Recombinant AAV Vectors: Characterization and Risk Assessment

J Fraser Wright. Biomedicines. .

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: AAV vectors; clinical trials; impurities.

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Conflict of interest statement

JFW is an inventor on patents relating to AAV vector technologies, has consulted to industry in the field of viral vector gene therapy, and is a co-founder of Spark Therapeutics.

Figures

Figure 1
Figure 1
Adeno-associated virus (AAV) vector and impurity levels during purification.
See this image and copyright information in PMC

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