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

[Shirley Entzminger]

 	T O D A Y . . .


 		   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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