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Retrovirus-mediated TCR Gene Transfer

Creative Biolabs develops various popular strategies to transfer TCR genes into T cells, one of which is mediated via retrovirus. With its high infection efficiency, stable recombinant gene expression ability and low immunogenicity, retroviruses have become the first choice in gene therapy researches, including some FDA-approved clinic trials. Our retrovirus-mediated TCR gene transfer solution consists of the construction of plasmid containing TCR gene, the generation of recombinant retroviruses and the production of virus particles with packing cells and the transduction TCR gene into T cells. Retroviruses infect target cells by binding of the viral envelope protein to cell surface receptors.

Retrovirus-mediated TCR gene transfer

Figure: Retroviral gene transfer to generate tumor-specific T cells

Retroviruses can be found in almost all animals including chickens, mice, goats, primate, humans and fish. In clinical gene therapy, retroviral vectors are one of the most preferred transfer systems. Up to date, vectors derived from gamma-retroviruses such as murine leukemia viruses (MLVs) have been widely used for gene transfer into human T cells. Retroviral viral DNA can be stably incorporated into host genome and propagated in daughter cells, so retroviral vectors are appropriate tools to perform long-term expression of the transgene, achieving therapeutic efficacy. After entering host cells, the single-stranded RNA genome of retroviruses is released into the cytoplasm and converted into a double-stranded DNA by virus-encoded reverse transcriptase. Followed by which, the viral DNA forms pre-integration complex, a large nucleoprotein structure containing proteins which are important for nuclear localization and facilitate to insert viral DNA into the host genome. One of the most important barriers during the use of retrovirus vectors is they are unable to transduce nonproliferating target cells, while in many gene therapy protocols, target cells such as T cells are quiescent and induction of cell proliferation is to be avoided. Now, improved retroviral systems including retrovirus packing cells and vector components have been researched and developed to express cloning and functional genomics.

The most popular strategies used for TCR gene transfer:

Viral vectors: Retroviral vectors
Lentiviral vectors
Electroporation

References:

  1. Youngsuk Yi, et al. Current Advances in Retroviral Gene Therapy. Curr Gene Ther. 2011 Jun; 11(3):218-28.
  2. Toshio Kitamura, et al. Retrovirus-mediated gene transfer and expression cloning: Powerful tools in functional genomics. Exp Hematol. 2003 Nov;31(11):1007-14.
  3. Els Verhoeyen, et al. Lentiviral Vector Gene Transfer into Human T Cells. Christopher Baum (ed.), Methods in Molecular Biology, Methods and Protocols, vol. 506.

To discuss your demands or to request a proposal, please contact us by info@creative-biolabs.com.

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CONTACT US

USA
45-1 Ramsey Road, Shirley, NY 11967, USA
Tel: 1-631-871-5806
Fax: 1-631-207-8356
Email:

Europe
Ringstrasse 4, 64401 Gross-Bieberau, Germany
Tel: 44-207-048-3343

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