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Gene transfer optimization for treating genetic disorders

Date:
March 4, 2014
Source:
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health
Summary:
Controlled gene transfer into different target cells by means of specific surface markers is significantly more efficient than gene transfer without this assistance. Gene therapies using lentiviral transfer of genetic information can thus be optimized. Lentiviruses, which belong to the family of retroviruses, are used as vectors to exchange genetic material in cells and can be used to replace a defective gene as defined by gene therapy. Increasing the efficiency of such a treatment poses a major medical challenge: the virus should specifically track the target cells, but the number of virus used should be as low as possible.

Controlled gene transfer into different target cells by means of specific surface markers is significantly more efficient than gene transfer without this assistance. Gene therapies using lentiviral transfer of genetic information can thus be optimized. These findings were reported by scientists of Helmholtz Zentrum München in the Biomaterials journal.

Lentiviruses, which belong to the family of retroviruses, are used as vectors to exchange genetic material in cells and can be used to replace a defective gene as defined by gene therapy. Increasing the efficiency of such a treatment poses a major medical challenge: the virus should specifically track the target cells, but the number of virus used should be as low as possible.

A research team led by Dr. Ines Höfig and Dr. Natasa Anastasov from the Institute of Radiation Biology (ISB) at Helmholtz Zentrum München in cooperation with Sirion Biotech GmbH in Munich and the Fraunhofer Institute in Aachen has now developed an adjuvant which enhances the effect of the virus transduction. Thus the transfer into the target cells is optimized without additional toxicity.

Surface molecules fuse viruses with target cells

The scientists equipped the viruses with additional surface molecules that facilitate the attachment of the viruses to their target cells. The surface molecules consist of a glycoprotein which is fused to an antibody fragment. This antibody fragment detects the surface receptors of specific target cells, such as EGFR+ or CD30+, and binds to these.

Higher transduction rate -- less virus used

"Through this specific binding to the target cell we can enhance three fold the transduction rate (transfer of the viruses into the target cells)," said research group leader Anastasov. "Thus, the transduction efficiency is improved, and at the same time fewer transfer viruses are needed."

In further studies, analog to the established system, suitable antibody fragments shall be evaluated for specific surface markers of various target cells, e.g. for bone marrow stem cells and immune cells. Gene therapy can thus be used as a treatment for specific genetic disorders (e.g. metachromatic leukodystrophy, Wiskott-Aldrich syndrome).


Story Source:

The above story is based on materials provided by Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. Note: Materials may be edited for content and length.


Journal Reference:

  1. Höfig, I. et al. Systematic improvement of lentivirus transduction protocols by antibody fragments fused to VSV-G as envelope glycoprotein. Biomaterials, March 2014 DOI: 10.1016/ j.biomaterials.2014.01.051

Cite This Page:

Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. "Gene transfer optimization for treating genetic disorders." ScienceDaily. ScienceDaily, 4 March 2014. <www.sciencedaily.com/releases/2014/03/140304071200.htm>.
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. (2014, March 4). Gene transfer optimization for treating genetic disorders. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2014/03/140304071200.htm
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. "Gene transfer optimization for treating genetic disorders." ScienceDaily. www.sciencedaily.com/releases/2014/03/140304071200.htm (accessed October 20, 2014).

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