BindCraft generates novel peptides to improve gene therapy vectors

AAV vectors have been successfully applied for several therapeutic applications, reaching clinical practice during the past few years. However, the natural serotypes that are typically used for gene therapy have the disadvantage to target a broad range of different cells and tissues. Because of this, high vector doses need to be injected into patients and there is an increased risk of side effects as the vector also targets cells or tissues that are not primarily involved in the disease.

To address this problem, we generated a ‘de-targeted’ AAV vector no more able to transduce cells in the dish by mutating key amino acids responsible for its primary interaction with glycans. Next, miniproteins were designed using BindCraft to bind a selected receptor on the cell surface. When modified by incorporating these peptides into the capsid, AAV gained the ability to transduce only the cells expressing the targeted receptor. We are currently further harnessing this approach to generate novel, more specific AAV vectors either as research tool or for ‘precision’ gene therapy.