Thursday, June 6, 2013
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Humanized shark variable
new antigen receptors (VNARs)
versions of VNARs could be used to bind protein epitopes that are difficult
to access using traditional antibodies. VNARs are a class of small,
immunoglobulin-like molecules from the shark immune system. A VNAR specific
for human serum albumin (ALB)
was isolated from the spiny dogfish shark, and humanized variants were
generated by substituting over 60% of the antibody's non-complementarity-determining
region (CDR) residues with those from a human antibody sequence. In vitro
immunoassays showed that the lead humanized VNAR retained its specificity and
ability to bind human serum ALB. Crystal structures in complex with human
serum ALB showed that the VNARs bound in a manner distinct from that of
previously described VNARs. Next steps could include generating humanized
shark VNARs against known disease targets.
Inc. and H.
Lundbeck A/S have partnered to develop shark VNARs to treat
SciBX 6(22); doi:10.1038/scibx.2013.560
Published online June 6, 2013
Patent and licensing status
Kovalenko, O.V. et al.
J. Biol. Chem.; published online April 30, 2013;
Contact: Oleg V. Kovalenko, Pfizer Inc., Cambridge, Mass.
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