Insights into HIV-1 virion makeup could improve gene therapy

Published on February 18, 2013 at 5:15 PM · No Comments

By Helen Albert, Senior medwireNews Reporter

medwireNews: A discovery about how the HIV-1 virion packages genomic (g)RNA may help researchers to improve the efficacy of gene therapy.

Researchers led by Eric Arts, from Case Western Reserve University in Cleveland, Ohio, USA, found that an RNA element known as the genomic RNA packaging enhancer (GRPE) chooses the type and amount of gRNA that gets packaged into individual virions.

Two types of viral vector, adenoviruses and lentiviruses (eg, HIV), have been developed to treat patients with a variety of diseases. However, adenoviral vectors have a limited lifespan and have to be given frequently, while lentiviral vectors are stable, but fail to deliver enough genetic material to their target cells.

As reported in Cell Host and Microbe, Arts and colleagues believe that a lack of knowledge about GRPE in lentiviruses converted to gene therapy vectors has led to the inefficient delivery of genetic information observed to date. As part of the current study, Arts and team inserted GRPE into a lentiviral vector, resulting in a significant increase in the amount of gRNA packaged and an improved ability to deliver to target cells.

Previous research showed that a packaging element known as ψ is needed for HIV-1 RNA encapsidation to occur, but it was less clear how specific types and amounts of gRNAs were selected for packaging. The discovery of GRPE clarifies this issue.

Arts and co-authors found that deleting or disrupting GRPE led to large reductions in the amount of gRNA packaged in HIV-1 virions and their infectivity. They believe that using lentiviral vectors containing GRPE has the potential to improve the delivery and success of gene therapy over current methods five-to-10 fold.

"Using lentivirus for gene transfer appears to be a safe option," said Stanton Gerson, Director of the Case Comprehensive Cancer Center at Case Western University, who was not involved in the study, in a press statement. "This discovery could greatly advance the recent successes ongoing in cancer and childhood congenital diseases."

He added: "Improvements in the technology of gene delivery identified by Arts and his colleagues could lead to many more effective studies that help patients with many different diseases, including cancer."

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