Recent Patents on DNA & Gene Sequences (Discontinued) - Volume 1, Issue 3, 2007

Redox control is an important determinant of cellular function and viability. The thioredoxin system is a major antioxidant system that influences cellular redox state, stimulates cell growth, inhibits apoptosis, activates numerous transcription factors and regulates immune function. Both over and under expression of the thioredoxin system can result in a disease phenotype and therefore it has been the target of many therapeutic strategies. High levels of thioredoxin expression have been associated with aggressive cancers, poor patient prognosis and resistance to some chemotherapy treatments. In contrast, low levels of thioredoxin can cause diseases that develop because of an imbalance between antioxidant systems and oxidative stress, stimulants. A number of recent patents and patent applications have been published that describe inventions that either inhibit or enhance thioredoxin functionality. Thioredoxin expression levels have been decreased through antisense approaches and thioredoxin functionality has been inhibited by synthetic compounds or by stimulating the production of VDUP1, a natural thioredoxin inhibitor. Strategies designed to enhance thioredoxin functionality include the addition of recombinant thioredoxin or using gene delivery to treat hepatic disease, inflammatory bowel disease, cardiovascular disease, skin damage or cystic fibrosis. Mutant thioredoxin molecules that target specific pathways or that exhibit increased stability are also utilised.

The tightly regulated expression of p53 contributes to genomic stability and transcription of the p53 gene is induced prior to cells entering S-phase, possibly as a mechanism to insure a rapid p53 response in the event of DNA damage. We have previously described the cloning of an additional 1000bp of upstream p53 sequences that we have demonstrated play a role in the regulated expression of p53. As described in earlier reports we identified that a member of the C/EPB family of transcription factors may play a role in regulating p53. A particular C/EBPβ isoform, C/EBPβ-2, efficiently binds to the p53 promoter and induces its expression in a fashion that reflects the pattern of p53 expression seen as cells are induced to enter S-phase and is absent from cells that are defective in proper p53 regulation. We conclude from these findings that C/EBPβ-2 plays a central role in regulating p53 transcription during the transition into S-phase. The recent development of novel compounds that restore wild-type p53 activity to tumor cells raises the possibility that understanding the means by which p53 gene expression is deregulated in tumors cells could likely lead to the development of novel therapeutic strategies designed to return p53 to its normal expression.

In recent years, many pharmaceutical and biotechnology companies have shifted their drug development for infectious diseases from antibacterial to antiviral discovery. This trend reflects the large population involved in viral diseases, the need for chronic or long-term treatment, and significant unmet needs. In particular, human immunodeficiency virus, hepatitis C virus (HCV), and hepatitis B virus have been the focus of drug development, representing important areas of future growth. This report provides an overview of the most recent patents relating to HCV molecules as targets for therapeutic intervention, outlining the key drug targets and steps where pharmacological intervention can have a favorable therapeutic benefit. Historically, HCV drug development has been hampered by the lack of reliable cell culture systems and animal infection models. However, early research studies have identified new models of HCV infection, and the better acknowledgment of the viral lifecycle have allowed the identification of several highly promising targets, including protease, helicase, polymerase or inhibitors of virus attachment, which are considered drug candidates that can potentially change the treatment of HCV.

In mammalian ovary, follicular development in mammals is regulated by the complex process including endocrine, paracrine and autocrine. During the last decade, the role of growth factors in ovarian folliculogenesis has been extensively studied in mammals. In particular, a growing body of evidence indicates that the vascular endothelial growth factor (VEGF) system plays a key role in follicular development and atresia in the woman, rodents and domestic animal species. More recently, the bone morphogenetic protein (BMP) and growth differentiation factor (GDF) that belong to TGF-β family have been shown to be involved in the regulation of follicle growth. In this paper, we will essentially consider the role of these growth factor systems in mammalian ovary. Moreover, we will review recent patents associated with ovarian follicular development in mammals.

In the course of evolution, venomous animals developed highly specialized venomous systems that provided for drastic increase in hunting and defense efficiency. Venoms of a vast number of animal species represent complex mixtures of compounds such as ions, biogenic amines, polyamines, polypeptide neurotoxins, cytolytic peptides, enzymes, etc. that exert different functions. Natural toxins are sequentially variable molecules that are very stable structurally and produce pronounced biological effects on molecular targets. High activity made them very attractive in terms of novel structure discovery and characterization. In the present review we draw attention to the structure of polypeptide molecules preferably in the 2-12 kDa molecular mass range produced by various venomous animals that were published in patent literature. The structures were reviewed on the basis of functional relation to molecular targets. We also compared the sequence information from patents with Uniprot and other protein databanks to define structures that were patented but missing from the public databases.

Many recent studies have addressed the impact of gene patents and methods of gene delivery on downstream research and innovation. The field of gene therapy has progressed over the last 10 years due to the rapid advancement in delivery technology. Efficient delivery of genes into target cells depends on the absence of cell injury, oncogenic mutation or inflammation. Gene transfer technology saw a significant boost by the applications of in vivo electroporation. This approach is versatile and safe and can be used to deliver nucleic acid fragments, oligonucleotides, siRNA, and plasmids to a wide variety of tissues, such as skeletal muscle, skin and liver. Many have applied this approach in autoimmune or inflammatory diseases, for the intratumoral delivery of therapeutic vectors, or for systemic delivery of endocrine hormones, hematopoietic factors, antibodies, enzymes, or numerous other protein drugs. This technique has been found to strongly boost DNA vaccination against infectious agents or tumor antigens. in vivo Electroporation has been performed in humans. This review will focus on the intellectual property revolving around recent developments in the area of electroporation, including devices and methodology for various applications.

A new horizon is lit up by exploiting plant viruses as the vectors to deliver foreign genes into plants for various purposes such as production of valuable pharmaceutical proteins, to understand pathogenesis of a plant virus, and to establish gene silencing for blocking, for example, production of an undesirable intermediate metabolite in a metabolic pathway. Here, the recent patents concerning the design of new gene vectors on the basis of the genomes of the viruses including Tobacco mosaic virus (TMV), Potato virus X (PVX), Tobacco rattle virus (TRV), Cowpea mosaic virus (CPMV), Bean Yellow dwarf virus (BeYDV), Beet soil-borne mosaic virus (BSbMV) and Potato mop top virus (PMTV) will be reviewed. Also, applications of the recently designed vectors for production of foreign proteins such as human lysosomal enzymes expressed from TMV-based vectors, human and animal viral vaccines expressed from CPMV-based vectors and glucose oxidase from BSbMV-based vector will be reported. In addition, gene silencing capabilities of the vectors based on PVX and the seed coating gene delivery system will be considered.

Toll-like receptors (TLRs) are members of pattern recognition receptor family involved in sensing and eliciting responses against many pathogens based primarily on their molecular patterns. TLRs are major markers of innate host defence and are evolutionarily conserved across various species from insects to humans. These type I transmembrane proteins expressed by innate immune cells (dendritic cells, macrophages, NK cells), cells of the adaptive immunity (T and B lymphocytes) and non-immune cells (epithelial, endothelial cells and fibroblasts) orchestrate the adaptive immunity to combat the infections. Thirteen TLRs have been identified in mammals and the overlap between them allows recognition of a diverse range of pathogens. Recent research reviewed here is focused on modulating the innate immunity in mammals through use of TLR agonists in combating infections. Single nucleotide polymorphisms (SNPs) of TLR genes associated with incidence and course of infectious diseases and inherited diseases in human population are also reviewed.

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