Recent Patents on DNA & Gene Sequences (Discontinued) - Volume 3, Issue 3, 2009

The search for a classic biomarker for prostate cancer has been on for a very long time, and it is still elusive. Despite the extensive and prolonged use of the prostate-specific antigen (PSA) as a screening tool for prostate cancer, many clinicians still identify its limitations in the grading of tumors, and monitoring of response to treatment. These limitations are based on the concealment of cancer by low levels of PSA, and over diagnosis and over treatment that are resultant of excessively high levels of antigens. To overcome these limitations, a plethora of candidate biomarkers have been investigated and identified. Regrettably, none of these putative biomarkers has shown ideal utility for prostate cancer detection and prognostication. In spite of these, various patents have been filed and granted for several of these biomarkers. The discovery of an exclusive marker for prostate cancer may be mired by the heterogeneity of the disease, since the molecular mediators of the disease are linked with its etiopathogenesis. Thus the search for biomarkers of prostate cancer must recognize its etiology and downstream mediators. In this review, PCGEM1, a patented prostatespecific non-coding RNA gene with an upregulated transcription in African American malignancy will be discussed in relationship to the etiology of prostate cancer.

Other than its well-recognized effects on reproductive physiology, estrogen has important actions in a wide variety of other body systems with important examples including bone, blood vessels and the heart. These effects are seen in both females and males. Investigators have hypothesized that genetic variants in the genes coding for estrogen signalling proteins may cause variable sensitivity to the hormone and influence an individual's estrogen-sensitive phenotypes. The most obvious candidate genes are the estrogen receptors alpha and beta (ERα and β). However, the regulation of these genes is complex and not well understood. Furthermore, their coding exons, and regulatory sequences are dispersed across large segments of the genome. A number of common polymorphisms have been identified in both ERα and ERβ, with variable degrees of evidence of their direct biological significance and their association with human disease. The identification of genetic variations associated with altered estrogen response is of potential public health importance. Insights may be gained into the pathogenesis of estrogen sensitive diseases such as osteoporosis, breast cancer and cardiovascular disease contributing to the development and application of newer therapies for these disorders. Furthermore, genetic variants that alter sensitivity to estrogen may affect both therapeutic and harmful responses to exogenous estrogen administered in the form of the oral contraceptive pill or hormone replacement therapy. This clinical significance has led to the publication of a number of patents which will be reviewed.

Methodologies for identifying as well as discriminating between different strains of Mycobacterium tuberculosis and their differing degrees of drug resistance are crucial for the correct and more efficacious administration of treatment and vaccines. This is emphatically so now that the immunogenic and phylogeographic correlates to the genomes of different strain families are beginning to be mapped out. The patents here discussed start with those aimed at detecting M. tuberculosis from other mycobacterial species by polymerase chain reaction-mediated comparative sequence analysis, taking advantage of previously unrecognized points of variability in the genome and of the rpoB gene. Patents on methods for strain discrimination describe particular nucleotide sequences able to distinguish between different infections, specific microarray probes, polymorphisms in variable number of tandem repeats loci and molecular mass and base composition analysis. Diagnostic kits for detecting antimicrobial resistance recur to oligonucleotide probes for various loci identified to be involved in conferring resistance. An innovative application of molecular inversion probes (MIPs) as a resource-maximizing tool for SNP discovery and genotyping is also mentioned. These patents provide valuable methods by which to detect M. tuberculosis for both clinical and research purposes, and provide the basis for their future adaptations aimed at a less costly and increased worldwide usage.

The maintenance of T cell homeostasis requires the balance of both positive and negative regulatory signals of T cell proliferation. The herpesvirus entry mediator (HVEM) is a TNF superfamily receptor member, which provides a stimulatory signal following engagement with LIGHT (TNFSF14) on T cells. In contrast, HVEM can also provide an inhibitory signal to T cells when it binds the B and T lymphocyte attenuator (BTLA), a ligand member of the Immunoglobulin (Ig) superfamily. Thus, HVEM may be viewed as a molecular switch, capable of facilitating both stimulatory and inhibitory cosignaling in T cells. Substantial evidence from both human disease and from experimental mouse models has indicated that dysregulation of the LIGHT-HVEM-BTLA cosignaling pathway can cause inflammation in the lung and in mucosal tissues. Moreover, the discovery that two different viruses, human cytomegalovirus (HCMV) and herpes simplex virus (HSV) both target the LIGHT-HVEM-BTLA system as part of their immune evasion strategies suggests that this cosignaling pathway may prove useful in manipulating host immunity. Indeed, the LIGHT-HVEMBTLA system may constitute an important molecular target for biopharmaceutical intervention as it holds the key for controlling both costimulatory and coinhibitory signals. Thus, the rational manipulation of this pathway should aid in the development of safer and more effective drugs for a wide range of autoimmune-related inflammatory disorders. To this end, this review provides a summary on several recent patents associated with the LIGHT-HVEM-BTLA cosignaling system.

The field of epilepsy genetics is contentious, particularly when it concerns the common epilepsies. More than a dozen loci have been suggested, the result of either linkage analysis and/or association analysis, but few of these findings have been replicated, let alone proven, and those that have are mostly for rare forms of epilepsy. Molecular genetics has revolutionised the understanding of epilepsy genetics and is beginning to have a significant clinical impact. Technological advances have resulted in new high-throughput approaches that promise to further our understanding of the molecular genetics of the epilepsies. The patents discussed in this review highlight the important discoveries that have contributed to our understanding of epilepsy genetics and provide valuable information as to where research in this area will be heading in the future. This knowledge not only informs clinicians about the biology of the epilepsies but also has important consequences for clinical practice and genetic counselling.

Over the past decade, rapid progress in the molecular studies of cardiac ion channels and stem cells biology has led to efforts to create a biological pacemaker to supplement the widely-used electronic pacemaker. This review focuses on the main concepts of cardiac pacemaker activities in different heart regions and the patented approaches to design a working biological pacemaker. The gene-based and cell-based approaches to meet the requirements of a working biological pacemaker are reviewed. Possible future development and precautions for creation of an effective biological pacemaker superior to the electronic counterpart are discussed.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), the ninth member of the proprotein convertase (PC) family, has emerged as a potential target for reducing plasma low-density lipoprotein cholesterol (LDL-c) levels. PCSK9 post-transcriptionally downregulates the low-density lipoprotein receptor (LDLR) in the liver by binding to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR and thereby controls the level of LDL-c in plasma. Some of its natural mutations called gain-of-function mutations cause hypercholesterolemia and coronary heart disease (CHD), whereas loss-of-function mutations in the PCSK9 gene are associated with hypocholesterolemia. This review summarizes the current understanding of PCSK9 and recently published patent and patent applications on methods and techniques that may efficiently reduce plasma LDL-c levels through inhibiting PCSK9 expression by antisense oligonucleotides, small interference RNAs (siRNAs), specific antibodies, or other small molecules.

Goats/sheep are important in the animal agriculture of China. Distribution of these animals in China is closely related to the economic performance and ecological conditions in the specific regions. Comparative genome study is popular in China although the sheep and goat genome information are not well sequenced. Expression Sequence Tags (EST) are well developed in skin and ovary organ. Transgenic productions are focused on goat milk chiefly. Microsatellite DNA and mtDNA polymorphism were used to analyze the genetic structure mainly and some of them were used to detect the Quantitative Trait Loci(QTL) of goat and sheep. Only the candidate gene markers are used as Marker Assisted Selection (MAS) and integrated into Best Linear Unbiased Prediction (BLUP) selection strategy in goat and sheep nucleus breeding flock according to different breeds. Although some studies have proposed direct selection on the individual gene loci responsible for the genetic variation in some traits, there are 20 goat/sheep gene patents in the past decade. Some patents on gene with extremely broad claims will shadow over the commercialization of these gene and fill the blank of the gene patents in goat/sheep fields.

Improving essential amino acids or protein content, along with other phytochemicals in food crops, will affect a great portion of the world’s population, especially in developing countries where rice grain is the main source of protein. Malnutrition, including deficiencies in protein/energy, iron/zinc, vitamin A, and iodine, causes a total 24,000 deaths per day worldwide. The problem is severe where rice is the major staple food. Protein deficiency involves both the quantity (amount) and quality (the content in essential amino acids) of the dietary protein. Various interventions, such as distribution, fortification, dietary diversification, and measures against infectious diseases, have been applied to reduce deficiency disorders. The problem, however, remains unsolved. Developing genetically novel lines with elevated content of essential amino acids together with other health benefit components becomes more feasible for the enhancement of breeding techniques, genomics, molecular manipulations, and genetic engineering. Advancement in basic genetic and genetic engineering has resulted in successful enrichment of some essential amino acids, such as lysine (Lys), tryptophan (Trp), and methionine (Met). Successful genetic enhancement has been largely through enrichment of grain Lys and to some extend Trp in maize. Since rice is the main source of calories and protein intake for billions of people, enhancing essential amino acids in rice represents a tremendous challenge. This paper will discuss and review the current status in basic genetics, molecular genetics, and genetic engineering associated with the enhancement of amino acids and other health benefit components in major grain crops. Patents and future efforts associated with enhancing nutritional quality of the grain will also be reviewed as a concerted effort to solve the malnutrition problem and improve the quality of life worldwide.

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