Stem cells, gene delivery

Deng Y, Guo X, Yuan Q, Li S. Efficiency of adenoviral vector mediated CTLA4Ig gene delivery into mesenchymal stem cells. Chin Med J (Engl) 2003 116 1649-1654. 

Brown, A.B., Yang, W., Schmidt, N.O., Carroll, R., Leishear, K.K., Rainov, N.G., Black, P.M., Breakefield, X.O., Aboody, K.S. (2003). Intravascular delivery of neural stem cell lines to target intracranial and extracranial tumors of neural and non-ncural origin. Hum Gene Ther, 14, 1777-85. 

Saraf A, Hacker MC, Sitharaman B et al (2008) Synthesis and conformational evaluation of a novel gene delivery vector for human mesenchymal stem cells. Biomacromolecules 9 (3) 818-827... 

Another novel cardiovascular therapy that has recently come into play is the use of stem cell delivery. These approaches have thus far involved the use of gene delivery mechanisms to essentially force embryonic stem cells into cardiomyocyte differentiation with the goal of producing a cardiac pace-making cell (Arruda et al., 2004). Researchers are also developing methods for utilizing seeded adult mesenchymal stem cells as an implanted base to act as a depot for the delivery of localized gene therapies (Arruda et al., 2004). 

Meinel, L., Hofmann, S., Betz, O., Fajardo, R., Merkle, H.P., Langer, R., Evans, C.H., Vunjak-Novakovic, G., and Kaplan, D.L. "Osteogenesis by human mesenchymal stem cells cultured on silk biomaterials Comparison of adenovirus mediated gene transfer and protein delivery of BMP-2". Biomaterials 27(28), 4993-5002 (2006b). 

Viruses Viruses provide a unique and extremely efficient method of insertion of genes into mammalian cells, such as human bone marrow stem cells. SV 40, adenovirus, vaccine virus, and polyomavirus have been used as gene transfer vectors. A non-replicating adenoviral vector that efficiently infects human cells has recently been developed. The essential feature of a retroviral gene delivery system is the presence of an RNA copy of the replacement gene that is packaged in a viral particle, capable of specific and efficient entry into the cytoplasm of a cell. A retrovirus consists of... 

Since the OTC trial, there has been rapid advancement in vector development with marked improvements in the safety (and efficacy) of new viral delivery systems. There is also a better understanding of the immunological responses to gene therapy vectors. The adverse events in the SCID trial are more recent. They appear to be a likely result of the choice of vector (retrovirus) and the ex vivo selection strategy used to modify the affected stem cells of the SCID patients. The risk benefit ratio for gene therapy treatment of these children is still deemed favorable in light of the fact that without treatment, they would not be alive. 

Lu, Y. (2004) Recombinant adeno-associated virus as delivery vector for gene therapy — a review. Stem Cells Dev 13 133—145. 

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