Characterizing Viruses: From Deadly Pathogens to the Workhorses of Gene Therapy

Speaker:

Akash Bhattacharya, PhD

Abstract:

Viruses are a few megabytes of genomic information wrapped inside a protein shell and sometimes a lipid coat. They exist in the shadow of the tree of life, requiring the metabolic capabilities of a host to propagate. Yet viruses have successfully stalked every clade of life, infecting almost every extant species. The impact of viruses ranges from decimating entire populations to colonizing them or simply infiltrating the very genomic pool of a species and continuing to exist purely in the form of endogenous retroviruses. Virology is the youngest of the biological sciences- and it has finally come of age in the 21st century.

The physical characterization of the virion and its interaction with the host cell is a focal point of both pathogenic and therapeutic virology. Every step of the virus-host infection cycle is a druggable target. In this webinar, Dr. Bhattacharya will discuss the role of analytical ultracentrifugation (AUC) in uncovering the biophysics of these therapeutic targets. We will discuss typical case examples, including one where AUC is used to determine the dimerization affinity of SARS-CoV-2 protease.

In the second half of this webinar, Dr. Bhattacharya will discuss the role of Recombinant Adeno Associated Virus (rAAV) vectors as one of the most promising mechanisms for therapeutic gene delivery. A typical phase III clinical trial can require up to ~ 1018 bioactive AAV capsids (aka Enhanced Transduction Units or ETUs). The production of such large quantities of bioactive AAV particles is fraught with production challenges such as maintaining integrity and maximizing efficiency of the delivery vehicle. Known as the gold standard in assessing the quality of AAV preps, AUC can distinguish between degraded capsids, empty, full and partially loaded capsids with exceptional resolution. The webinar will conclude by comparing AUC measurements to other techniques and how to use the results to optimize process development.