Problems with Gene Therapy

Miller, A.D., The problem with cationic liposome/micelle-based non-viral vector systems for gene therapy, Current Medicinal Chemistry, 2003, 10, 1195-1211. 

Their proposal won FDA approval, the first gene therapy trial everto inject AAV. In June 1999 the clinical team injected the first patient with genetically altered AAV. The procedure was uneventful. Two more patients followed. As the team reported in the March 2000 issue of Nature Genetics, at the suboptimal dose used in the study, meant only to detect manifest safety problems, the first three patients showed no untoward effects and no detectable antibodies [6]. Within 12 weeks after the injec-(Continued on next page)... 

Thomas CE, Ehrhardt A, Kay MA (2003) Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet 4 346-358... 

Gene therapy constitutes a novel form of drug delivery.51 To employ their full potential as therapeutic agents, genes have to be delivered in a very specific and efficient way to their cellular targets. In the field of gene therapy, the problems and high risks associated with the use of virus particles for efficient delivery of... 

The major problem of gene therapy is the low transduction efficiency in vivo. For the application to cancer this problem is exacerbated by the inefficient vascularization and high interstitial pressure in malignant tumors, which limit the accessibility for any kind of vector. One possibility to address this problem is the use of viruses that are able to replicate in vivo and thereby spread throughout the tumor tissue. This approach is not only useful for the improved delivery of therapeutic proteins but seems particularly appealing if combined with the intrin-... 

---