• Le 08 janvier 2018

Une revue intéressante venant juste de paraître dans Molecular Therapy Methods & Clinical Development :

"Pharmacology of recombinant adeno-associated virus production"

Magalie Penaud-Budloo, Achille François, Nathalie Clément, Eduard Ayuso

Recombinant adeno-associated viral vectors (rAAV) have been used in more than 150 clinical trials with a good safety profile and significant clinical benefit in many genetic diseases. In addition, due to their ability to infect non-dividing and dividing cells and to serve as efficient substrate for homologous recombination, rAAV are being used as a tool for gene-editing approaches. However, manufacturing of these vectors at high quantities and fulfilling current good manufacturing practices (GMP) is still a challenge and several technological platforms are competing for this niche. Herein, we will describe the most commonly used upstream methods to produce rAAV, paying particular attention to the starting materials (input) used in each platform and which related impurities can be expected in final products (output). Most commonly found impurities in rAAV stocks include: defective particles (i.e. AAV capsids that do contain the therapeutic gene or are not infectious), residual proteins from host cells and helper viruses (adenovirus, Herpes simplex virus or baculoviruses) and illegitimate DNA from plasmids, cells or helper viruses that may be encapsidated into rAAV particles. Given the role that impurities may play in immunotoxicity, this article reviews the impurities inherently associated with each manufacturing platform. Methods & Clinical Dev