Analytical methods to characterize recombinant adeno-associated virus vectors and the benefit of standardization and reference materials.

Recombinant adeno-associated virus (rAAV) is an increasingly important gene therapy vector, but its properties present unique challenges to critical quality attribute (CQA) identification and analytics development. Advances in, and ongoing hurdles to, characterizing rAAV proteins, nucleic acids, and vector potency are discussed in this review. For nucleic acids and vector potency, current analytical techniques for defined CQAs would benefit from further optimization, while for proteins, more complete characterization and mapping of properties to safety and efficacy is needed to finalize CQAs. The benefits of leveraging reference vectors to validate analytics and CQA ranges are also proposed. Once defined, CQA specifications can be used to establish target parameters for and inform the development of next generation rAAV processes.