Recent patents on DNA & gene sequences最新文献

RNA interference (RNAi) is one of the most significant recent breakthroughs in biomedical sciences. In 2006, Drs. Fire and Mello were awarded the Nobel Price for Physiology or Medicine for their discovery of gene silencing by double-stranded RNA. Basic scientists have used RNAi as a tool to study gene regulation, signal transduction and disease mechanisms, while preclinical drug development has gained from its use in target validation and lead optimization. RNAi has also shown promise in therapeutic applications, and several synthetic RNA molecules have entered clinical trials. The family of short regulatory RNA molecules, including small interfering RNAs (siRNAs) and micro-RNAs (miRNAs), offers many possibilities for the innovative mind. When conventional small molecule inhibitors cannot be used, RNAi technology offers the possibility for sequence-specific targeting and subsequent target gene knockdown. Currently the major challenges related to RNAi -based drug development include delivery, off-target effects, activation of the immune system and RNA degradation. Although many of the expectations related to drug development have not been met thus far, these physiologically important molecules are used in several applications. This review summarizes recent patent applications concerning micro-RNA biology. Despite the somewhat unclear intellectual property right (IPR) status for RNAi, there are many possibilities for new inventions, and much remains to be learned from the physiology behind gene regulation by short RNA molecules.

Colorectal cancer (CRC) is the third most common cancer in the world. Early diagnosis of colorectal cancer is the key to reducing the death rate of CRC patients. Predicting the response to current therapeutic modalities of CRC will also have a great impact on patient care. This review summarizes recent advances and patents in biomarker discovery in CRC under five major categories; including genomic changes, expression changes, mutations, epigenetic changes and microRNAs. The interesting patents include: 1) a patent for a method to differentiate normal exfoliated cells from cancer cells based on whether they were subjected to apoptosis and DNA degradation; 2) A model (PM-33 multiple molecular marker model) based on expression changes of up-regulation of the MDM2, DUSP6, and NFl genes down-regulation of the RNF4, MMD and EIF2S3 genes, which achieved an 88% sensitivity, and an 82% specificity for CRC diagnosis; 3) gene mutations in PTEN, KRAS, PIK3CA for predicting the response to anti-EGFR therapies, a common drug used for CRC treatment; 4) patents on epigenetic changes of ITGA4, SEPT9, ALX4, TFAP2E FOXL2, SARM1, ID4 etc. and many key miRNAs. Finally, future directions in the fields were commented on or suggested, including the combination of multiple categories of biomarkers and pathway central or network-based biomarker panels.

White rot fungi have an enzymatic system producing oxidative and hydrolytic enzymes that act on the degradation of certain components of the cell wall. They can be applied in several technological processes, such as paper industry, bio-fuels and environmental pollution. Laccases are multi-copper enzymes of wide substrate specificity and high non-specific oxidation capacity that use molecular oxygen to oxidize various aromatic compounds, and are highly relevant biotechnological applications. In this review, we present some significant patents on laccase production and recombinant DNA technology for diverse biotechnology applications.

One of the many controversies surrounding large-scale biofuel production is the diversion of land and other resources that might otherwise be used for food crops. Recent innovations will lead to a second generation of biofuel crops that can co-exist with food crops with little or no competition. Feedstocks from these bio-energy crops will be used to produce liquid fuel from cellulose, the most abundant polymer on the planet. Cell walls of higher plants are mainly composed of cellulose, hemicellulose, and lignin polymers. Cellulose and hemicellulose are polysaccharides with obvious value for biofuel production. However, lignin, while vital for plant growth and development, is widely known to negatively impact conversion efficiencies. Biomass pre-treatment, which is aimed at lignin removal, is not straightforward, and presents one of the major scientific and technical challenges and expenses associated with secondgeneration biofuel production. Scientific breakthroughs associated with altering the expression of key genes in the lignin biosynthetic pathway of biomass crops is a promising path toward solving this problem, and will likely impact the feedstock patent landscape in the near future. This review summarizes some of the recent and most important issued patents and patent applications associated with lignin-modification genes and methods of developing transgenic plants with altered lignin content and composition.

Research on antimicrobial peptides has gained pace to exploit their potential and ability to replace conventional antibiotics. Antimicrobial peptides are important members of the host defense system, as they have a broad ability to kill microbes. Antimicrobial peptides and proteins form an important means of host defense in eukaryotes. Large antimicrobial proteins (>100 a.a.), are often lytic, nutrient-binding proteins or specifically target the microbial macromolecules. Small antimicrobial peptides act by disrupting the structure or function of microbial cell membranes. A multitude of antimicrobial peptides has been found in the epithelial layers, phagocytes, and body fluids of multicellular animals including humans. Aside from their role as endogenous antibiotics, antimicrobial peptides have functions in inflammation, wound repair, and regulation of the adaptive immune system. In this review, we discuss recent patents relating to antimicrobial peptides. These patents are related to the method of identifying peptides that have antimicrobial activity, including the papillosin antimicrobial peptide and its encoding gene, the antimicrobial peptide isolated from Halocynthia aurantium, retrocyclins, and the use of cathelicidin LL-37 and its derivatives for wound healing. These patents provide valuable information that could be useful in the identification of antimicrobial peptides and the exploitation of their therapeutic potential.

The antiproliferative and antitumor effect of leaf ribonuclease was tested in vitro on the human ML-2 tumor cell line and in vivo on athymic nude mice bearing human melanoma tumors. The antiproliferative activity of this plant ribonuclease in vitro studies was negligible. In the experiments in vivo a significant decrease of the tumor size, however was observed. From nucleases the mung bean nuclease (PhA) was studied first from nucleases. The antitumor effect of this enzyme on ML2 human tumor cell line was almost non-effective. However, significant antitumor activity was detected on human melanoma tumors in vivo. The antitumor effect of black pine pollen nuclease (PN) tested in vitro was also negligible. On the other side, in the experiments in vivo a significant decrease of the human melanoma tumor size was observed too. Recombinant plant nucleases of tomato (TBN1) and hop (HBN1) (submitted to patenting under no. PV 2008-384;Z7585) were isolated to homogeneity and examined for their antitumor effects and cytotoxicity. Although antiproliferative effects of both recombinant nucleases were not significant on the ML-2 cell culture in vitro, the nucleases were strongly cytostatic in vivo after their administration intravenously as stabilized conjugates with polyethylene glycol (PEG). Recombinant both nucleases were as effective against human melanoma tumors as previously studied pine pollen (PN) and mung bean nucleases and their effects were reached at about ten times lower concentrations compared to the use of bovine seminal RNase (BS-RNase).

ColE1-like plasmids constitute the most popular vectors for recombinant protein expression. ColE1 plasmid replication is tightly controlled by an antisense RNA mechanism that is highly dynamic, tuning plasmid metabolic burden to the physiological state of the host. Plasmid homeostasis is upset upon induction of recombinant protein expression because of non-physiological levels of expression and because of the frequently biased amino acid composition of recombinant proteins. Disregulation of plasmid replication is the main cause of collapse of plasmid-based expression systems because of a simultaneous increase in the metabolic burden (due to increased average copy number) and in the probability of generation of plasmid-free cells (due to increased copy number variation). Interference between regulatory elements of co-resident plasmids causes comparable effects on plasmid stability (plasmid incompatibility). Modulating plasmid copy number for recombinant gene expression aims at achieving a high gene dosage while preserving the stability of the expression system. Here I present strategies targeting plasmid replication for optimizing recombinant gene expression. Specifically, I review approaches aimed at modulating the antisense regulatory system (as well as their implications for plasmid incompatibility) and innovative strategies involving modulation of host factors, of R-loop formation, and of the timing of recombinant gene expression.

Type 2 diabetes mellitus has become a world wide extended disease, and while insulin insensitivity is an early phenomenon partly related to obesity, pancreas beta-cell function declines gradually over time already before the onset of clinical hyperglycaemia. Therefore, drugs able to stimulate or enhance insulin secretion will moderate hyperglycemia and then reduce the occurrence of later complication of the disease. Current strategies in type 2 diabetes include sulphonylurea compounds, GLP1, exendin 4 and DPP4 inhibitors and GK activators. Since many diabetic patients still exhibit poor glycemic control, other fail to respond to the treatment, and some develop serious complications, more effective treatments for diabetes than those mentioned above remain challenging for modern research. Then, the present review will focus on existing approaches and novel patents targeting beta-cell, with special emphasis in those related with the glucose-induced insulin secretion process. The management of this disease includes not only diet and exercise, but also utilization of antihyperglycemic new drugs, gene therapy strategies and combinations of novel insulin releasers and secretagogues.

The importance of RNA in vital cellular events like gene expression, transport, self-splicing catalytic activity etc., renders them an alternative target for drugs and other specific RNA binding ligands. RNA targets gain significance for the fact that targeting DNA with therapeutics sooner leads to drug resistance and severe side effects by impairing essential function of the genes. However the unique structural features of the RNA facilitate targeting in two different approaches: 1) targeting the catalytic activity of the RNA (ribozyme) 2) exploiting the catalytic functions of ribozyme to target other cellular RNA of our interest. The first strategy leads to the inhibition of ribozyme catalysis by small molecule drugs or RNA binders. This would be very much effective in terms of unique target for specific RNA binders as ribozymes are present in certain pathogens and nonexistent in humans. Apart from targeting ribozymes by therapeutics the second strategy explores that ribozymes by itself can act as therapeutics to correct the defective cellular RNA by trans-splicing activity and are renowned as equivalent as that of any gene therapy for genetic disorders or it can be a "gene inhibitor" as it can cleave the target RNA. In this series many trans-splicing ribozymes are engineered and patented for their vital catalytic activity. However here the focus has been given to recent patents on group I intron-derived trans-splicing ribozymes, and their catalytic functions as therapeutics are discussed.