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.
Delivery and success of gene therapy for human cells has the
potential of increasing five to ten times with the introduction of the
GRPE into the lentiviral vector.
"Using lentivirus for gene transfer appears to be a safe option,"
said Stanton L. Gerson, MD, director of the Case Comprehensive Cancer
Center and the Asa and Patricia Shiverick- Jane Shiverick (Tripp)
Professor of Hematological Oncology at Case Western Reserve School of
Medicine and director of the Seidman Cancer Center at University
Hospitals Case Medical Center, who is not involved in the study. "This
discovery could greatly advance the recent successes ongoing in cancer
and childhood congenital diseases. 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. Its impact could be felt in a few short years."
Ultimately, introducing GRPE elements into viral vectors could
enhance the ease and effectiveness of gene therapy, which typically uses
transplanted human stem cells. Enhanced gene therapy and other
improvements in targeted cell delivery might eliminate the need for stem
cells and allow cells to be administered directly into patients.
Journal Reference:
- Mastooreh Chamanian, Katarzyna J. Purzycka, Paul T. Wille, Janice S. Ha, David McDonald, Yong Gao, Stuart F.J. Le Grice, Eric J. Arts. A cis-Acting Element in Retroviral Genomic RNA Links Gag-Pol Ribosomal Frameshifting to Selective Viral RNA Encapsidation. Cell Host & Microbe, 2013; 13 (2): 181 DOI: 10.1016/j.chom.2013.01.007
Courtesy: ScienceDaily
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