Abstract: Human gene therapy has made substantial progress since the initiation of the first clinical trials 20 years ago. Here, we summarized important applications of gene transfer protocols in the treatment of various human diseases using different viral vectors. Recent successful trials on the treatment of ocular diseases and inherited immune deficiencies are particularly encouraging and have raised hopes that human gene therapy as a standard treatment option will finally become a reality. While immune responses and insertional mutagenesis pose obstacles for this novel form of molecular medicine, continuous progress suggests that a wider range of diseases can be treated with gene therapy in the future. ... Read more

Abstract: Gene therapy for inherited retinal degeneration has made major advances toward the ultimate goal of reversing blindness in human patients. With significant advances in recombinant viral vector design, safety and efficacy profiles have greatly improved. Although these recent advances have been applied to many different retinal diseases, one retinal degenerative disease, Leber congenital amaurosis, appears to have the greatest potential for reversing blindness. In pre-clinical animal studies, gene therapy for Leber congenital amaurosis has demonstrated visual recovery. Recently, in landmark clinical trials, preliminary results have indicated safety and efficacy for the use of gene therapy in Leber congenital amaurosis, thus laying the foundation for continued use of gene therapy in other forms of inherited blinding disease. ... Read more

Abstract: Gene-directed enzyme prodrug therapy offers a new approach to treating some cancers. Clinical trials have been completed for brain and prostate cancers and the first product for post-surgical treatment of some brain tumors is awaiting marketing approval. Recent innovations provide a glimpse into the possible future evolution of a new gene medicine. ... Read more

Abstract: Despite the social stigma and manufacturing hurdles that come with using viruses as therapeutic tools, the molecular specificity offered by these bugs makes them too attractive to ignore. Still largely based on vaccines, viral vectors offer exciting tools to treat cancer or deliver specific genetic payloads to a desired tissue. Unfortunately, early clinical trials utilizing such vectors have been plagued with poor performance or even clinical toxicity most commonly associated with spurious genetic regulation and/or replication of the vector. Past efforts to control for unwanted toxicity have focused on modification of the receptor or use of tissue-specific genetic elements that added specificity to the transcriptional induction of the gene(s) of interest. While this has had some success, engineering receptors to control viral tropism often fails or results in a loss of replicative fitness. In addition, the use of tissue-specific promoter elements not only restricts the vector that can be used, bona fide small promoter elements are often not available for the desired target. With the caveats of viral vector-based therapeutics largely centered on a lack of in vivo control, the recent success of exploiting microRNA expression to limit viral tropism may breathe new life into the field. ... Read more

Abstract: Nanotechnology based on the use of submicronic particles of inorganic and/or organic origin has the potential to revolutionalize the clinical management of cancer; the possibility of real time monitoring of disease progression and effects of therapy is now real. Especially, iron oxide super paramagnetic nanoparticles have shown clinical utility in cancer imaging and drug delivery and some formulations are now FDA-approved for use in the clinic. The prospects of magnetic nanoparticles in cancer imaging and treatment are reviewed. ... Read more

Abstract: Hemophilia A is an X-linked bleeding disorder caused by defective coagulation Factor VIII (FVIII). Although the efficacies of existing treatment using purified or recombinant FVIII are good, there remain shortcomings in using this particular form of treatment. A few FVIII gene therapy clinical trials have been initiated with modest improvements recorded, but these are no longer being continued due to insufficient efficacy. However, with the progress in the development of gene delivery vectors and the availability of mouse and canine hemophilia A models, gene therapy of hemophilia A remains an area of hot pursuit. ... Read more

Abstract: The non-viral vectors and targeting methods offer some specific advantages. These include better safety profiles (lower toxicity and non-infectious properties) and the capacity to transfer large genes and low production costs. The clinical usefulness of non-viral methods has been hindered by their relatively low gene delivery and transgene expression efficiencies. However, recent problems in clinical trials using viral vectors renewed interest in non-viral technologies, particularly that the properties of non-viral vectors make them appear closer to the traditional pharmaceutics. ... Read more

Abstract: Gene therapy holds a great promise to prevent allograft rejection or to induce transplant tolerance. Many achievements in vector development have allowed the progression of this therapy to become more attainable in clinical transplantation. In this articles, the authors examine the exciting development in various vector technologies that allows this form of therapy to take the central stage of clinical transplantation. Also highlighted are various therapeutic strategies that might ultimately result in the realization of gene-based treatment in clinical transplantation. ... Read more

For many of the difficult-to-treat diseases, gene-based therapies and gene-based drug deliveries offer hope and excitement. In this issue of Discovery Medicine, articles describe the use of gene therapy to manipulate stem cells for treating heart diseases (Dr. Rosen et al. on page 18), to produce vaccines for the immunotherapy of cancer (Dr. Acres et al. on page 25 and Dr. Stevenson on page 37), and to fight HIV-1 infection (Dr. Egan on page 58).

However since their first use about two decades ago, gene therapies have remained experimental. Genes with therapeutic potential have been injected into test animals and patients ... Read more

A major obstacle to the development of gene therapy for cancer has been the inability to specifically and systemically deliver gene therapy vectors throughout the body to primary and/or metastasized tumor cells. Although intratumor injections of gene therapy vectors have sometimes been possible, no viral vector has been available that could be administered systemically and would selectively and efficiently target tumors without infection of normal tissues. Furthermore, even when locally injected, many viral vectors end up at high concentrations in the liver, because many cells of the body have low receptor numbers for some of the vectors in current use, ... Read more