Recent Patents on DNA & Gene Sequences (Discontinued) - Volume 2, Issue 1, 2008

Small nucleolar RNA molecules (snoRNA) comprise a special kind of non-coding RNAs involved in the maturation process of rRNAs, snRNAs, tRNAs and mRNAs. Traditionally, these molecules have been divided into two families depending on the type of conserved boxes that they harbour: box C/D and H/ACA snoRNAs. Both types of snoRNAs are found associated with proteins forming a complex called snoRNP. Although some of the snoRNPs of each family mediate endonucleolytic cleavages of pre-rRNA, most of them participate in nucleotide modification: 2'-Omethylated nucleotides in the case of C/D snoRNPs and pseudouridine in the case of H/ACA snoRNPs. Based on published patents, the purpose of this review is to show the biotechnological impact of these molecules, which rely on their special features: participation in the functionality of ribosome, specific location on cell, and abnormal expression in some diseases like cancer.

The questions surrounding patenting of DNA sequences encoding specific proteins are relatively well reviewed in the available literature. However, neither applications nor molecular cytogenetic techniques, which use these sequences as a probe, have been reviewed in the light of the patenting. Furthermore, the patenting of the use of numerous probes, which are produced on different types of repetitive genome elements (i.e. satellite DNA or telomeric DNA sequences) and those generated by chromosome microdissection has not been reviewed. Molecular cytogenetic techniques are one of the most applied in current bioscience (as to June 2007, over 40,000 papers in browseable scientific databases mention one or several molecular cytogenetic techniques). Therefore, reviewing recent patents in this field is of general interest for numerous researchers in different areas of biology and medicine. Here, we address world-wide patents on DNA sequences used as molecular cytogenetic probes and molecular cytogenetic techniques to define current state and perspectives of this biomedical direction.

The cDNA of RPS15 was cloned successfully for the first time from the Giant Panda using RT-PCR technology, which was also sequenced and analyzed preliminarily. The cDNA fragment is 442bp in size, containing an open reading frame (ORF) of 438bp encoding 145 amino acids. Alignment analysis indicates that the nucleotide sequence and the deduced amino acid sequence show a high homology to those of human and other mammalian species reported. Topology prediction shows there are two cAMP and cGMP-dependent kinase phosphorylation sites, one Ribosomal Protein S19 signature site, four N- myristoylation sites and five Casein kinase C phosphorylation sites in the RPS15 protein. Further analysis indicates that the expression sequence of RPS15 and the protein encoded are highly homologous to those of human and other mammals reported. The study is of significance to provide truthful and scientific data for studying the Giant Panda (Ailuropoda melanoleuca) at molecular level, especially for cloning and further researching the complete sequence of RPS15.

Real-time Polymerase Chain Reaction (PCR) is a quickly developing technology that has built upon the classic end-point PCR detection methods. In this article, we will review recent patents related to various chemistries used for nucleic acid detection during real-time PCR amplification. Real-time assay chemistries are subdivided into several main categories including DNA-binding agents, molecular beacons, hybridization probes, hydrolysis probes, and dye-primer based systems. Specific advantages and applications of each category are highlighted herein.

Research on ErbB receptors has spearheaded the rational cancer drug design, and ErbB1 (also known as EGFR) and ErbB2 are among the first clinically validated targeted therapies. Despite the fact that applicability of ErbB4 as a drug target is still uncertain, several patents involving utilization of ErbB4 have recently been issued. Manipulation of functions of ErbB4 may be therapeutically beneficial in cancer but also in psychiatric and cardiovascular disorders. In addition, analyzing expression or mutations of ErbB4 may provide prognostic or predictive value. Contents of ErbB4- related patents, as well as biology of ErbB4 and its alternatively spliced isoforms, will be reviewed in this article.

Eukaryote cells survey genomic integrity for DNA damage or incomplete replication. Aberrant structures being detected, checkpoint mechanisms are activated to slow down or arrest cell cycle progression, which allow the DNA damage to be repaired and the replication to be completed. In cancer development, precancerous cells overcome selective pressure to escape from blocked cell cycle progression, induced by checkpoint responses to DNA damage. Medical applications targeting the process of DNA damage would lead to efficient repairs of DNA damage or induction of cell death, which contributes to cancer detection, diagnosis and therapeutic approaches. In this article, the recent progress of our knowledge and patenting in modulation of DNA damage checkpoint especially by Rad9-Chk1 pathway is noted and possible application for cancer medicine is discussed.

RNA interference has been implicated in diverse biological process. It is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. The success of early studies of therapeutic RNAi in rodent models has generated considerable interest on the development of RNAi as a potential therapy. A number of recent patents have been published that deal with the use of siRNA as therapeutic tools for human diseases. In this review, I will comment on some of the patents issued on siRNA-based strategies for cancer, ocular diseases, cardiovascular disease, Alzheimer's disease, Parkinson's disease, bone healing, and monogenic diseases such as amyotrophic lateral sclerosis, Marfan syndrome or Huntingon's disease. Progress in developing RNAi-based drugs and potential obstacles will also be discussed.

Gene therapy is a promising therapeutic modality for the treatment of genetic disorders. Gene therapy has been able to correct many of the genetic diseases at the root of their cause by systematizing genetic information that encodes for all functions of every cell in our body. Recent studies have identified novel molecular targets for genetic disorders that can be used to deliver gene to the specific site. Gene therapy applications require safe and efficient method for gene transfer. Over the last decade, non-viral and viral gene therapy approaches have been tested in preclinical studies and human clinical trials. Gene delivery via conventional means by using viral vectors has several undesirable side effects such as insertion of mutational viral gene into the host genome and overwhelming immune and inflammatory responses. As compared to viral vectors, non-viral vehicles has received great attention due to their several favorable properties, including low toxicity and immunogenicty, resistance to nuclease, and their high affinity for DNA targets. Here, we describe how non-viral gene-transfer vehicles have been used and can be modified to target specific tissues for gene therapy. This review focuses on existing and emerging patents on non-viral based genetic engineering strategies for the delivery of therapeutic molecules or several approaches for genetic disorder treatment.

Acute aortic dissection (AAD) is a common fatal disease that affects the aorta and requires an urgent clinical intervention. A clinical feature of AAD is the characteristic tearing retrosternal pain often confused with that of myocardial infarction. In type A after Stanford, the biluminal progression is in the ascending aorta, the lethality of all untreated patients is about 50% within the first 48 hours. Most of AAD patients do not present a known connective tissue disorder. This makes the diagnosis more difficult and often late established. Similar as in myocardial infarction, a rapid test for the diagnosis establishment would be vitally helpful. This review summarizes, with examples taken from recent patents, novel strategies maintaining the development and validation of biomarkers of acute aortic dissection and compares them to known biomarkers of myocardial infarction.

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