Viruses replicate by introducing their genetic material into new host cells. In naturally-occurring viral infections, this genetic material provides instructions to the host cell for making more viruses. The potential for viruses to introduce genetic material (e.g., DNA) into cells has long been exploited for scientific and medical purposes by replacing the original viral genes with a therapeutic payload. Such viruses, reprogrammed to deliver a therapeutic payload, are known as “vectors.”

A virus known as “adeno-associated virus” (AAV) has been engineered into an efficient vector. AAV vectors have had the DNA encoding all of the viral genes deleted and replaced with a therapeutic payload, so there is no potential for them to replicate. Such vectors based on AAV have been tested in numerous human clinical trials.

We engineered an AAV vector to contain DNA encoding eCD4-Ig. Monkeys that received a single injection of this AAV vector into their quadriceps secreted eCD4-Ig into the bloodstream, and were completely protected from infection despite multiple intravenous injections of live virus. This initial proof-of-concept experiment demonstrated that a single injection of AAV encoding eCD4­-Ig can be effective as an alternative to conventional approaches for vaccinating against HIV.

We are also investigating the ability of a single injection of AAV that produces eCD4-Ig to suppress viral replication in someone who is already infected with HIV. Thus, AAV-produced eCD4-Ig may provide a backstop against viral resistance to other therapies, or even be a stand-alone, one-time intervention for treating HIV-infection.