Surface-Engineered Viral Vectors for Selective and Cell Type-Specific Gene Delivery

Recent progress in gene transfer technology enables the delivery of genes precisely to the application-relevant cell type ex vivo on cultivated primary cells or in vivo on local or systemic administration. Gene vectors based on lentiviruses or adeno-associated viruses can be engineered such that they use a cell surface marker of choice for cell entry instead of their natural receptors. Binding to the surface marker is mediated by a targeting ligand displayed on the vector particle surface, which can be a peptide, single-chain antibody, or designed ankyrin repeat protein. Examples include vectors that deliver genes to specialized endothelial cells or lymphocytes, tumor cells, or particular cells of the nervous system with potential applications in gene function studies and molecular medicine.

TrendsNumerous receptor-targeted viral gene vectors have been described during the past years using distinct cell surface proteins for cell entry that are selectively expressed on defined cell types instead of their natural broadly expressed receptors.Receptor-targeting strategies based on directed evolution or rational engineering have been established. The latter is equally applicable to non-enveloped and enveloped vectors involving the destruction of natural receptor usage followed by the addition of a high-affinity ligand mediating attachment to the desired surface protein.Receptor-targeted vector particles can be as selective for their targeted cell type as antibodies for their antigen when applied systemically or locally in preclinical studies.Receptor targeting opens up novel concepts in gene therapy and the cell type-specific delivery of genetic material in life sciences.