Aug
12
Mon
2013
Invited Talk: ColoAd1- An oncolytic adenovirus derived by directed evolution @ Acharya Hall
Aug 12 @ 2:07 pm – 2:30 pm

TerryHermistonTerry Hermiston, Ph.D.
Vice President, US Biologics Research Site Head, US Innovation Center Bayer Healthcare, USA


ColoAd1 – An oncolytic adenovirus derived by directed evolution

Attempts at developing oncolytic viruses have been primarily based on rational design. However, this approach has been met with limited success. An alternative approach employs directed evolution as a means of producing highly selective and potent anticancer viruses. In this method, viruses are grown under conditions that enrich and maximize viral diversity and then passaged under conditions meant to mimic those encountered in the human cancer microenvironment.  Using the “Directed Evolution” methodology, we have generated ColoAd1, a novel chimeric oncolytic adenovirus. In vitro, this virus demonstrated a >2 log increase in both potency and selectivity when compared to ONYX-015 on colon cancer cells. These results were further supported by in vivo and ex vivo studies. Importantly, these results have validated this methodology as a new general approach for deriving clinically-relevant, highly potent anti-cancer virotherapies.  This virus is currently in clinical trials as a novel treatment for cancer.

Terry (1) Terry (2)

Aug
14
Wed
2013
Plenary Talk: Combined Crystallography and SAXS Methods for Studying Macromolecular Complexes @ Amriteshwari Hall
Aug 14 @ 9:38 am – 10:19 am

JeffPerryJeff Perry, Ph.D.
Assistant Professor, University of California, Riverside


Combined Crystallography and SAXS Methods for Studying Macromolecular Complexes

Recent developments in small angle X-ray scattering (SAXS) are rapidly providing new insights into protein interactions, complexes and conformational states in solution, allowing for detailed biophysical quantification of samples of interest1. Initial analyses provide a judgment of sample quality, revealing the potential presence of aggregation, the overall extent of folding or disorder, the radius of gyration, maximum particle dimensions and oligomerization state. Structural characterizations may include ab initio approaches from SAXS data alone, or enhance structural solutions when combined with previously determined crystal/NMR domains. This combination can provide definitions of architectures, spatial organizations of the protein domains within a complex, including those not yet determined by crystallography or NMR, as well as defining key conformational states. Advantageously, SAXS is not generally constrained by macromolecule size, and rapid collection of data in a 96-well plate format provides methods to screen sample conditions. Such screens include co-factors, substrates, differing protein or nucleotide partners or small molecule inhibitors, to more fully characterize the variations within assembly states and key conformational changes. These analyses are also useful for screening constructs and conditions that are most likely to promote crystal growth. Moreover, these high throughput structural determinations can be leveraged to define how polymorphisms affect assembly formations and activities. Also, SAXS-based technologies may be potentially used for novel structure-based screening, for compounds inducing shape changes or associations/diassociations. This is addition to defining architectural characterizations of complexes and interactions for systems biology-based research, and distinctions in assemblies and interactions in comparative genomics. Thus, SAXS combined with crystallography/NMR and computation provides a unique set of tools that should be considered as being part of one’s repertoire of biophysical analyses, when conducting characterizations of protein and other macromolecular interactions.

1 Perry JJ & Tainer JA. Developing advanced X-ray scattering methods combined with crystallography and computation. Methods. 2013 Mar;59(3):363-71.

Jeff (1)