A research team from Case Western Reserve University School of Medicine has discovered an approach that could make gene therapy dramatically more effective for patients.
Led by professor Eric Arts, PhD, the scientists discovered that the process of gene therapy is missing essential elements thereby reducing the effectiveness of this treatment. Re-introducing this element into their model system suggests that improvements for gene therapy areon the horizon.
The findings are detailed in the article, "A new genomic RNA packaging element in retroviruses and the interplay with ribosomal frameshifting," published today in the journal Cell Host & Microbe.
Advances in gene therapy offer promising treatment for genetic abnormalities, tumors and resistance to toxic chemotherapies. Such therapy has been used to treat cystic fibrosis, hemophilia, muscular dystrophy and sickle cell anemia.
But a failure to distribute enough modified genetic information to the patient's body has prohibited gene therapy from being more widely used.
Gene therapy relies mainly on viruses—which transport genomes inside the cells they infect—to deliver genetic material into a patient's cells. The virus-driven delivery tools are called "viral vectors."
Unfortunately, the success rate of viral vectors is uneven. For instance, adenoviruses, a cause for the common cold, and lentiviruses, such as HIV-1, are routinely converted into viral vectors. But adenovirus vectors don't last long, so therapy must be frequently re-administered. And lentiviral vectors, while stable, fail to deliver genetic material to enough defective human cells.
Arts, a professor of medicine in the Division of Infectious Diseases and HIV Medicine, learned that lentiviral carriers lack sufficient genetic material necessary for treatment.
HIV-1, when converted from virus to lentiviral vector, loses a specific RNA element required to pack its "container" with its own genetic material to be effective. After identifying the problem, researchers introduced the element into a lentiviral vector, successfully and significantly improving the quality and quantity of the gene therapy.
Arts and colleagues named the genetic element, Genomic RNA Packaging Enhancer element (or GRPE). During virus production, GRPE coordinates the production and filling of the container with the genetic material of HIV-1, or the desired human gene.