Abstract: Given improvements in viral vector design, production and efficiency of transduction in the central nervous system (CNS), as well as increased knowledge of neuropathological mechanisms in neurological disorders, success in treating a CNS disorder with gene transfer seems inevitable. Several different vector systems have been studied extensively and the adeno-associated viral vector system has been utilized in most early stage clinical trials in neurological disorders. Other vector systems, such as lentivirus, adenovirus, and herpes simplex virus are also viable vector platforms that should fill significant clinical niches based on their specific characteristics. In addition to the choice of the appropriate vector, the proper choice of transgene for the appropriate strategy to treat a neurological disorder is also critical. The example of glial cell line-derived neurotrophic factor ligands to treat Parkinson's disease is used to illustrate the importance of the interface between interpretation of pre-clinical data and consideration of the natural history of the disorder. This interface dictates the proper design of clinical trials that are capable of testing whether the treatment is actually successful. ... Read more

Abstract: Oncolytic virotherapy is an emerging therapeutic modality for the treatment of cancer. It entails construction of viruses with the ability to selectively target and lyse tumor cells. This branch of therapy has significantly advanced in the past decade, heralded by the development of several novel viruses. Despite the initial success of oncolytic virotherapy in the preclinical setting, however, this treatment modality remains hindered by several obstacles. First, failure to achieve effective viral delivery to targeted tumor beds is a well known limitation. Second, the virus-neutralizing mechanisms of the host immune system, which are in place to protect from viral pathogens, may also hinder the therapeutic potential of virotherapy. One approach to tackling these shortcomings is the use of cell-based carriers to both help with delivery of the virus and shield it from immunosurveillance. Stem cells have recently surfaced as a potential cell-based candidate for delivery of virotherapy. Their unique migratory and immunosuppressive qualities have made them an exciting area of investigation. The focus of this review is to discuss the benefits of stem-cell-based delivery of oncolytic virotherapy and its role in cancer treatment. ... Read more

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: Late stage hormone refractory prostate cancer (HRPC) is presently incurable. Novel alternatives such as cytoreductive Gene Directed Enzyme Prodrug Therapy (GDEPT) offer great hope: The potential for in situ amplification of cytotoxicity due to GDEPT-associated "bystander effects" has special appeal for patients with prostate cancer, the prostate being dispensable. In this overview, recent developments in various GDEPT systems for treating prostate cancer are described. Research related to the enhancement of in situ GDEPT delivery and prostate cancer-targeting of viral vectors, is reviewed. The scope and progress of synergies between GDEPT and other treatment modalities, traditional and alternate, are discussed. ... Read more

Abstract: The success of organ transplantation is one of medicine's finest accomplishments. Ironically, this same success has led to a dilemma in that there are simply too few donor organs available to treat the millions of patients that would benefit from their procurement and transplantation. The answer(s) to this shortage will likely come from transplanting specific cells, i.e., cell transplantation, tailored to replace equally specific functions normally served by damaged tissues or organs. To facilitate successful clinical outcomes, technologies derived from areas such as nanoscience will play a more prominent role and will be discussed in this review. ... 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