Stem Cell Gene Therapy

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Ferguson, C., Larochelle, A., and Dunbar, C.E. 2005. Hematopoietic stem cell gene therapy dead or alive Trends in Biotechnology 23(12), 589-597. 

Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Aiuti, A., Slavin, S., Aker, M., Ficara, F., Deola, S., Mortellaro, A., Morecki, S., Andolfi, G., Tabucchi, A., Carlucci, F., Marinello, E. et al. (2002). Science, 296 (5577) 2410-2413. 

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Finally, lentiviral vectors have been shown to transduce human embryonic stem cells. Therefore, this type of gene-therapy vector might also be used in stem cell-based therapies. 

In somatic cell gene therapy, a DNA sequence is inserted into a somatic cell to correct a mutation. Cells may be removed from the patient for manipulation and subsequent reinsertion (ex vivo therapy), or they may be manipulated without removal fi om the patient (in vivo therapy). Ideally, cells with a very long life span (e.g., bone marrow stem cells) are treated, but other cells (e.g., lymphocytes) are sometimes more practical targets. 

Present guidelines of the National Institutes of Health (NIH), which supports much of the gene therapy research, allows use of stem cells in therapy but... 

Haviernik, P. and Bunting, K. D. 2004. Safety concerns related to hematopoietic stem cell gene transfer using retroviral vectors. Current Gene Therapy, 4, 263-276. 

To circumvent this problem, vectors that are based on lentiviruses have been developed. In contrast to prototypic retroviruses, lentiviruses do not require cell division for integration. Gene-therapy vectors have been developed from a broad spectrum of lentiviruses including human immunodeficiency vims (HIV), simian and feline immunodeficiency vims as well as visna/maedi vims. The most widely used lentiviral vector system is based on HIV-1. These vectors can efficiently transduce a broad spectrum of dividing and nondividing cells including neurons, hepatocytes, muscle cells, and hematopoietic stem cells [1,2]. 

Stem CeU-vs, T Cell-Based Gene Therapy Strategies for HIV-Infection. 278... 

Bai J, Rossi J, Akkina R (2001) Multivalent anti-CCR ribozymes for stem cell-based HIV type 1 gene therapy. AIDS Res Hum Retroviruses 17 385-399 Bai J, Sui J, Zhu RY, TaUarico AS, Gennari F, Zhang D, Marasco WA (2003) Inhibition of Tat-mediated transactivation and HIV-1 replication by human anti-hCychnTl intrabodies. J Biol Chem 278 1433-1442... 

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