The emergence of Advanced Therapy Medicinal Products (ATMPs), including cell and gene therapy medicinal products (GTMPs), promises significant progress in the treatment, mitigation and potential cure of many diseases, including genetic diseases and cancer.
Gene therapy products aim to cure a disease by replacing or fixing a faulty gene or a mutated gene, or delivering a new gene where it is missing. However, these rapidly developing technologies are complex and very different to traditional biopharmaceutical products.
In the field of Gene Therapy, recombinant adeno-associated viruses (rAAVs), initially discovered as a contaminant of adenovirus preparations, are the most widely used delivery vehicle for therapeutic administration of transgenes due to their high transduction efficiency, high levels of gene expression and favorable safety profile.
As AAV capsid proteins are critical for viral infectivity and the AAV vector potency, complete characterization of the constituent Virus Particles (VPs) of AAV vectors, including their sequences and post-translational modifications (PTMs), is highly recommended. For example, it has been shown that deamidation of a number of Asparagine residues can have a significant impact on transduction activity and can also be an early factor in terms of loss of vector activity. In depth structural characterization of viral proteins is therefore essential to ensure AAV product quality and consistency.