Research Group Developing Lentiviral Vectors for Treatment of Hemophilia

Researchers incorporated the CD47 protein in LV vectors to inhibit their destruction by macrophages.

In addition to several adeno-associated viral (AAV) vector–based gene therapies under development for the treatment of hemophilia, researchers at the San Raffaele Telethon Institute for Gene Therapy in Italy are focused on a hemophilia gene therapy based on lentiviral vectors (LVs).


One promising AAV-based gene therapy is being developed by Spark Therapeutics (recently acquired by Roche). The efficacy of the treatment appears to decrease over time, however. Because most humans have a naturally developed immunity to AAV, these therapies can sometimes be ineffective. LVs, which are derived from the HIV virus, are expected to be less subject to these problems. However, lentiviral vectors can also be cleared from the body by white blood cells (hepatic and splenic phagocytes) before they can have a therapeutic effect.


To overcome this problem, the scientists used LV vectors with the CD47 protein incorporated into their surfaces. This protein is known to inhibit the destruction of LVs by white blood cells.


When the LVs with high levels of CD47 were injected intravenously into monkeys, they were observed to be more resistant to phagocytosis and less susceptible to detection by antigen-presenting cells than normal LVs. These LVs also transferred the therapeutic agent to monkeys with hemophilia B without causing toxicity.


The researchers also believe that integrating the CD47 protein into lentiviral vectors could reduce the required dosage level and reduce the potential for side effects.



David Alvaro, Ph.D.

David is Scientific Editorial Director for That’s Nice and the Pharma’s Almanac content enterprise, responsible for directing and generating industry, scientific and research-based content, including client-owned strategic content. Before joining That’s Nice, David served as a scientific editor for the multidisciplinary scientific journal Annals of the New York Academy of Sciences. He received a B.A. in Biology from New York University and a Ph.D. in Genetics and Development from Columbia University.