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Making Gene Therapy Safer Using Self-inactivating LTRs

Date:
April 2, 2009
Source:
Journal of Clinical Investigation
Summary:
Several patients in gene therapy clinical trials have developed leukemia as a result of their treatment. The underlying cause of leukemia is thought to be that the viral vectors used to carry the therapeutic gene into cells (gamma-RVs) integrate into the genome of the cells disrupting the natural control of cancer-associated genes (a process known as insertional mutagenesis).

Several patients in gene therapy clinical trials have developed leukemia as a result of their treatment. The underlying cause of leukemia is thought to be that the viral vectors used to carry the therapeutic gene into cells (gamma-RVs) integrate into the genome of the cells disrupting the natural control of cancer-associated genes (a process known as insertional mutagenesis).

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By analyzing specific elements of gamma-RVs and another type of viral vector, LVs, in a tumor-prone mouse model, a team of researchers, at San Raffaele-Telethon Institute for Gene Therapy, Italy, has now provided evidence that LVs are substantially less likely to cause insertional mutagenesis and tumors than gamma-RVs.

Further, they found that modifying an element (known as the LTR) of both LVs and gamma-RVs such that it is self-inactivating (SIN) further improved safety. The authors therefore conclude that SIN viral vectors should be the preferred choice in future gene therapy trials.

In an accompanying commentary, Ute Modlich and Christopher Baum, at Hannover Medical School, Germany, discuss the clinical importance of these data and the numerous questions that they pose for future research.

The research is published in the March 23, 2009, issue of the Journal of Clinical Investigation.


Story Source:

The above story is based on materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal References:

  1. Montini et al. The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI37630
  2. Ute Modlich, Christopher Baum. Preventing and exploiting the oncogenic potential of integrating gene vectors. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI38831

Cite This Page:

Journal of Clinical Investigation. "Making Gene Therapy Safer Using Self-inactivating LTRs." ScienceDaily. ScienceDaily, 2 April 2009. <www.sciencedaily.com/releases/2009/03/090324213208.htm>.
Journal of Clinical Investigation. (2009, April 2). Making Gene Therapy Safer Using Self-inactivating LTRs. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2009/03/090324213208.htm
Journal of Clinical Investigation. "Making Gene Therapy Safer Using Self-inactivating LTRs." ScienceDaily. www.sciencedaily.com/releases/2009/03/090324213208.htm (accessed December 20, 2014).

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