A major challenge faced by the pharmaceutical industry has been how to rationally design and select protein molecules to create effective biologic drug therapies while reducing unintended side effects — a challenge that has largely been addressed through costly guess–and–check experiments. Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University offer a new approach, in a study published today in Biophysical Journal.

"I believe that biology is the technology of this century," said the study's senior author and Wyss Institute Core Faculty member Pamela Silver, Ph.D., who is also Professor in the Department of Systems Biology at Harvard Medical School. "But in order for that to be true in protein drug therapy, we must make drug discovery and development cheaper, faster and more predictable, with a higher potency for targets while eliminating side effects on healthy cells."

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Merging expertise from computer science and synthetic drug design, the new model reveals that the drug efficacy of fusion–protein therapies depends on the geometric characteristics of a drug's molecular components. Use of the model could potentially replace the need to physically make and test new biologic drug designs, cutting down timelines and costs associated with drug development.

The engineered fusion proteins are created by attaching a specific antibody to a specific therapeutic protein by a "linker" made of rigid DNA strands. The antibody, a protein itself used as a targeting tool, is selected based on what types of cells the therapeutic portion is intended to treat. As the antibody finds its target, such as a receptor on a cancerous or otherwise infected cell, the therapeutic protein simultaneously attaches to another receptor and triggers mechanisms to disrupt the cell's behavior. The efficacy of these new types of drugs depends on how well the two components of the fusion protein work together — that is, how well they each attach to their intended receptors at the same time.

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