ABSTRACT Self-inactivating retroviruses are an attractive vector choice for long term and stable expression of therapeutic genes because of their ability to integrate into the host genome. However, their utility as a human therapeutic platform is dependent on stringent criteria for safety and efficacy. Therefore, targeting the vector to a specific cell or tissue type is of paramount importance. Numerous virus-engineering strategies have been developed that either modify the viral surface glycoproteins or regulate transgene expression in a tissue-specific manner. The former, termed transductional targeting, involves modifying the viral glycoproteins that are responsible for binding to specific cellular receptors and facilitating entry into the host cell. The goal of this strategy is to develop a targeted, injectable retroviral based vector that will deliver the transgene to a specific cell or tissue type while leaving non-target tissue unharmed. Recently, the field has seen a technical advance with the demonstration that retroviruses can be pseudotyped with the envelope glycoproteins of the measles virus. The measles hemagglutinin (H) protein is responsible for receptor recognition, and the fusion (F) protein catalyzes lipid membrane mixing and viral entry. The natural tropism of the measles H protein for its receptors has been completely eliminated, allowing retargeting by the display of ligands such as growth factors or single-chain antibodies (scFvs) on the C-terminal end. We summarize the progress to date with retargeting retroviral cores via pseudotyping with measles virus H and F glycoproteins.
Buy this Article
|