Abstract: The application of RNA interference-based gene silencing technologies has the potential to treat a variety of illness. Preclinical studies and some early clinical trials have already demonstrated the utility of small interfering RNAs (siRNAs) as a potential novel therapy for the treatment of cancer, viral infections, as well as a wide range of additional diseases. To be effective, an siRNA must be taken up by specific cells, enter the cytoplasm, and be loaded onto the Argonaute protein, the catalytic core of the RNA induced silencing complex (RISC) to direct the cleavage of the homologous transcripts. To meet this need, a variety of novel siRNA delivery strategies have been developed. As our understanding of the molecular mechanisms underlying the RNAi pathway has increased so has the ability to rationally design effective silencing and delivery strategies. This review will examine the latest advances in non-viral delivery of siRNA, with special reference to targeted siRNA delivery to specific target tissues and cell types in vivo in preclinical animal models. ... Read more

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: Herpes viruses have the capability of establishing a latent infection - persistence of the viral genome in the absence of the production of infectious virions. Under the right opportunities, such as immunocompromised AIDS patients and immunosuppressed transplant patients, the human cytomegalovirus can "wake up" from hibernation and wreak havoc. ... Read more

Abstract: There is a well-documented link between the central nervous system (CNS) and the immune system. Under stress, CNS releases stress hormones that perturb the balance and stability kept by many factions of the immune system, with serious health consequences. ... Read more

Successful gene therapy depends on the “bells and whistles” of the transgene delivery vectors, which ideally should not only deliver a large target transgene into mammalian cells, but also express the gene permanently. Among the current viral vectors, adenoviral (Ad) vectors and herpes simplex virus (HSV) type 1 (HSV-1) vectors have the capacity to deliver a large DNA segment (~150Kb) into cells but only enjoy transient transgene expression. On the other hand, adeno-associated viral (AAV) vectors can integrate transgenes into mammalian cell genomes for long-term gene expression but can only pack DNA of a limited size (~4.5kb). It is increasingly ... Read more