From unique challenges to inspired solutions: how vector engineering makes in vivo gene therapy possible

Abstract

Recent advances in designing safe and efficient viral vectors have spearheaded unprecedented growth in clinical trials and regulatory approvals for experimental gene therapies. Still, important challenges remain for gene therapies that require systemic administration into the circulation, including the patient’s immune response and the need for precise activation in the target cell population while sparing other tissues. Extensive research in engineering the vector’s external surface and genome has led to clever solutions, allowing novel in vivo therapies for previously untreatable genetic diseases such as spinal muscular atrophy and Duchenne muscular dystrophy to reach the clinic. In the future, we expect novel strategies, such as different viral vectors or non-viral delivery vehicles, to overcome the shortcomings of viral therapy.