i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists
<p>The paper describes a new approach to engineer antibodies to act as agonists for cell surface receptors, which has potential applications in developing new biotherapeutics. The authors developed a method to re-shape conventional Y-shaped antibodies into more compact, linear “i-shaped” antibodies (iAbs) by transplanting sets of mutations identified in naturally occurring broadly neutralizing antibodies against HIV. Adding a new approach to the antibody engineering tool box — iAb engineering.</p>
<p>Three sets of mutations termed iAbdx, iAbaff1, and iAbaff2 were engrafted into panels of 10 antibodies targeting OX40 and induced the iAb shape, as confirmed by negative stain electron microscopy. </p>
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