[Crib-list] SPEAKER: Benjamin Schubert | CRIBB Seminar | Friday, May 5, 2017 | TIME: 12:00 PM - 1:00 PM | Building 32, Room 155

[Shirley Entzminger]

 		   COMPUTATIONAL RESEARCH in BOSTON and BEYOND Seminar


DATE:		Friday, May 5, 2017
TIME:		12:00 PM  1:00 PM
LOCATION:	Building 32, Room 155  (STATA)
 		(32 Vassar Street, Cambridge)

     Pizza and beverages will be provided at 11:45 AM outside Room 32-155.



TITLE:		Population-specific design of de-immunized
 			protein biotherapeutics



SPEAKER:	BENJAMIN SCHUBERT  (Harvard Medical School)


ABSTRACT:

Immunogenicity is a major problem during the development of 
biotherapeutics since it can lead to rapid clearance of the drug and 
adverse reactions. The challenge for biotherapeutic design is therefore to 
identify mutants of the protein sequence that minimize immunogenicity in a 
target population whilst retaining pharmaceutical activity and structural 
stability. Current approaches are moderately successful in designing 
sequences with reduced immunogenicity, do not account for the genetic 
variation of the immune system in a specific population, and require 
costly experimental post-screening to guarantee structural and functional 
integrity.

Here, we will present a novel computational approach for de-immunization 
design using multi-objective combinatorial optimization that 
simultaneously optimizes the likelihood of a functional protein sequence 
at the same time as minimizing its immunogenicity tailored to a target 
population. We bypass the need for three-dimensional protein structure and 
molecular simulations to identify functional designs by generating 
sequences using a probabilistic model that has been used previously for 
mutation effect and structure prediction. We will demonstrate the method's 
potential based on initial results of a proof-of-principle study in which 
we redesigned Factor VIII, a replacement therapeutic used to treat 
hemophilia A.

===================================================================

Massachusetts Institute of Technology
Cambridge, MA


For information about the Computational Research in Boston and Beyond Seminar, 
please visit...

 			http://math.mit.edu/crib/



===
Shirley A. Entzminger
Administrative Assistant II
Department of Mathematics
Massachusetts Institute of Technology
77 Massachusetts Avenue
Building 2, Room 350A
Cambridge, MA 02139
PHONE:	(617) 253-4347
FAX:	(617) 253-4358
E-mail:	daisymae at math.mit.edu
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