Recent Patents on DNA & Gene Sequences (Discontinued) - Volume 4, Issue 2, 2010

DNA methylation is one of the mechanisms for the epigenetic control of gene expression. Alterations in the methylation status of genomic DNA can result in the silencing of genes. Such control is of significance for a wide range of biological processes, ranging from cellular differentiation during development, genomic imprinting and X-chromosome inactivation to the maintenance of genome stability. The cytosine in the genomic DNA is converted to 5-methylcytosine. The hypermethylation of some CpG islands in genomic DNA could result in gene silencing and hypomethylation can lead to transcription and gene expression. There has been a great interest in developing molecular techniques to analyze genomic DNA methylation at the CpG islands. The discovery that DNA treatment with sodium bisulfite converts the cytosine to uracil while keeping the 5-methycytosine intact has opened the door to a number of strategies to investigate genomic DNA methylation both at regional and global levels. A survey of recently patented methods to analyze DNA methylation indicated a range of inventions from simple PCR to high throughput based technologies. The disease diagnosis was the prominent application of DNA methylation detection for most of these methods. Future inventions will likely concentrate on genome-scale DNA methylation discovery.

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.

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.

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.

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.

The goal of immunoregulatory DNA vaccination is the antigen- and tissue-specific suppression of pathological inflammation that underlies immune-mediated inflammatory disorders like autoimmune diseases and allograft rejection. Recent patents and patent applications have applied immunoregulatory DNA vaccines in rodent model systems and human clinical trials using plasmid DNA coding for autoantigens such as insulin and glutamic acid decarboxylase for type 1 diabetes, myelin-associated proteins for multiple sclerosis, and heat sock protein 60 for rheumatoid arthritis. In these cases, the objective is to induce a homeostatic-like regulatory immune response to suppress pathological inflammation. In addition, patent applications have disclosed the use of DNA vaccines encoding the pro-inflammatory MIF cytokine and the CD25 IL-2 receptor subunit to interfere with the inflammatory process. Approaches have also been taken to improve DNA vaccination efficacy, including covalent modification of plasmid DNA, engineering secretion of vaccine-encoded antigen, and co-delivery of DNA coding for anti-inflammatory cytokines, a mutant co-stimulatory molecule, a growth factor, or a pro-apoptotic protein. Furthermore, a patent application has disclosed the use of a DNA vaccine previously shown to treat successfully an autoimmune disease to prolong allograft survival. Taken together, these patents and patent applications indicate a promising bench-to-bedside potential for immunoregulatory DNA vaccination applied to autoimmune diseases and allograft rejection.

The patents annotated in this section have been selected from various patent databases. These recent patents are relevant to the articles published in this journal issue, categorized by significant fields of gene therapy methods, process and techniques involved.