Nanobodies design for treatment of age-related diseases

Mohammad Mehdi Heidari1, Yuriy L. Orlov2
1Department of Biology, Faculty of science,Yazd University, Yazd, Iran, Heidarimm@yazd.ac.ir
2Novosibirsk State University, Novosibirsk, Russia, orlov@bionet.nsc.ru

The problem of the treatment of age related diseases such as Alzheimer disease demands development of new drug design strategies. Reagents that specifically recognize oligomeric morphologies of AОІ have potential diagnostic and therapeutic value. Nanobodies (Nbs) or Single-domain antibodies are the smallest antigen-binding fragments derived from heavy-chain-only antibodies. The E1 nanobody selectively recognizes naturally occurring AОІ aggregates produced in human AD brain tissue We discuss a method for the generation and binding optimization of VHHs that involves the grafting of the complementarity determining regions (CDRs) from already existing, non-camelid antibodies to VHH frameworks, followed by affinity maturation and target binding improvement using in silico site-directed mutagenesis.

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