jin rongsheng quotation

Published in Cell Reports, the paper is titled, “Structural insights into rational design of single-domain antibody-based antitoxins against botulinum neurotoxins.” Led by Rongsheng Jin, PhD, a professor in the Department of Physiology & Biophysics at the University of California, Irvine, School of Medicine, this paper describes how the team first identified the neutralizing epitopes of six anti-BoNT nanobodies (VHHs) based on their crystal structures, then harnessed the structural findings to rationally design bifunctional nanobodies. Different than ordinary nanobodies, bifunctional nanobodies are composed of two nanobodies that bind simultaneously to the toxins.

“In a nutshell, we establish a platform for structure-based rational design of bifunctional antitoxins against BoNTs,” said Kwok-ho Lam, the first author and a project scientist in the Jin lab. “BoNTs can be misused as a bioweapon and thus have been classified as Tier 1 select agents by the Centers for Disease Control and Prevention, which is why there is urgent need for antitoxins.”

“Currently, the only available antitoxin remedies are polyclonal antibodies from horse or human serum, which have known health risks and are in limited supply. Monoclonal antibodies are still under development,” said Jin. “And, while it isn’t necessarily a cause for worry, the increasingly popular therapeutic uses of BoNT products also create risks of possible botulism resulting from the medical treatments where they are used.”

Newswise — Irvine, Calif. — The Botox toxin has a sweet tooth, and it’s this craving for sugars – glycans, to be exact – that underlies its extreme ability target neuron cells in the body … while giving researchers an approach to neutralize it. A study co-led by Rongsheng Jin, professor of physiology & biophysics at the University of California, Irvine; Min Dong with Boston Children’s Hospital-Harvard Medical School; and Andreas Rummel with the Hannover Medical School in Germany, reveals an important general mechanism by which the pathogen is attracted to, adapts to and takes advantage of glycan modifications in surface receptors to invade motor neurons. Glycans are chains of sugars synthesized by cells for their development, growth, functioning or survival. Results appear June 13 in Nature Structural and Molecular Biology.

“Our findings reveal a new paradigm of the everlasting host-pathogen arms race, where a pathogen develops a smart strategy to achieve highly specific binding to a host receptor while also tolerating genetic changes on the receptor,” Jin said. “And to some extent, this mechanism by which the toxin attacks human is similar to the one that is utilized by some important broad-neutralizing human antibodies to fight viruses, such as dengue viruses and HIV.”

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