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Public release date: 14-Feb-2013[ | E-mail |
Share ] Contact: Jessica Studeny
jessica.studeny@case.edu
216-368-4692
Case Western Reserve University
Case Western Reserve researchers pinpoint RNA element missing from viral vectors
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 viruseswhich transport genomes inside the cells they infectto 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.
###
About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.
Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."
The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu
[ | E-mail | Share ] ?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Public release date: 14-Feb-2013[ | E-mail |
Share ] Contact: Jessica Studeny
jessica.studeny@case.edu
216-368-4692
Case Western Reserve University
Case Western Reserve researchers pinpoint RNA element missing from viral vectors
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 viruseswhich transport genomes inside the cells they infectto 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.
###
About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.
Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."
The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu
[ | E-mail | Share ] ?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2013-02/cwru-dih021213.php
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