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Information about MCT-485!

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MultiCell Technologies Files U.S. and International Patent Applications for the Treatment of Liver Cancer

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About MCT-485

MultiCell Technologies' MCT-485 is a very small noncoding double stranded RNA (dsRNA) possessing a unique mechanism of action, and is the first of a family of prospective cancer therapeutics. MultiCell owns rights to several issued U.S. and foreign patents and patent applications related to MCT-485.

RNA interference

RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing (PTGS), and quelling. Only after these apparently unrelated processes were fully understood did it become clear that they all described the RNAi phenomenon. Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNA interference in the nematode worm Caenorhabditis elegans, which they published in 1998.

Two types of small ribonucleic acid (RNA) molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference. RNAs are the direct products of genes, and these small RNAs can bind to other specific messenger RNA (mRNA) molecules and either increase or decrease their activity, for example by preventing an mRNA from producing a protein. RNA interference has an important role in defending cells against parasitic nucleotide sequences – viruses and transposons. It also influences development.

The RNAi pathway is found in many eukaryotes including animals and is initiated by the enzyme Dicer, which cleaves long double-stranded RNA (dsRNA) molecules into short double stranded fragments of ~20 nucleotide siRNAs. Each siRNA is unwound into two single-stranded (ss) ssRNAs, respectively the passenger strand and the guide strand. The passenger strand is degraded and the guide strand is incorporated into the RNA-induced silencing complex (RISC). The most well-studied outcome is post-transcriptional gene silencing, which occurs when the guide strand pairs with a complementary sequence in a messenger RNA molecule and induces cleavage by Argonaute, the catalytic component of the RISC complex. In some organisms, this process spreads systemically, despite the initially limited molar concentrations of siRNA.

RNAi is a valuable research tool, both in cell culture and in living organisms, because synthetic dsRNA introduced into cells can selectively and robustly induce suppression of specific genes of interest. RNAi may be used for large-scale screens that systematically shut down each gene in the cell, which can help to identify the components necessary for a particular cellular process or an event such as cell division. The pathway is also used as a practical tool in biotechnology, medicine and insecticides.[1]

http://en.wikipedia.org/wiki/RNA_interference

SiRNA

Small interfering RNA (siRNA) or silencing RNA is used in the gene silencing technique to suppress gene expression. siRNAs naturally occur in cells as a component of the post-transcriptional gene silencing (PTGS) apparatus. Soon after discoveryof siRNA in plant cells, scientists began using siRNAs in vitro to study gene expression.

Performing RNAi in invertebrates is reasonably easy because a simple transfection of long a dsRNA is enough to degrade the target mRNA. Vertebrate cells elicit a significant antiviral response when they detect the presence of a long dsRNA. Consequently, instead of knocking down the identified gene, the cell goes through apoptosis giving entirely undesirable results.

Commercial siRNA transfection services are offered by pre-clinical CRO Altogen Labs (www.altogenlabs.com)

Scientists havesolved the problem of antiviral response by utilizing small-sized siRNA. They are created by segmenting a long dsRNA. When generated appropriately synthetic siRNA are potent gene silencers, do not produce any significant antiviral response and exhibit remarkable specificity to the target mRNA. esearchers develop siRNA from long dsRNA by dicing small hairpin RNAs or long dsRNA sequences, which in effectis anRNase III family endoribonuclease enzyme . The dicer cuts a dsRNA into smaller siRNA segments that usuallyends with two base overhang .

siRNAs are often introduced in cell lines either through transfection or electroporation. Soon after being inserted in the host cell, siRNA molecules become a part of the RNA-induced silencing complex (RISC). Guided by the antisense strand of the siRNA, RISC degrades the targeted mRNA inhibiting its translation.
Appropriate assays are then performed to detect and gauge RNAi activity. Controls are normally set up so RNAi results can be properly compared.

The success of RNAi is dependant on correct delivery of siRNA in appropriate amount at a time when it will brings about the maximum expected response. Such precisioncan be tricky. Off-targeting by siRNAs proves lethal and poses analytical issues at times. Researchers are looking for better ways of designing and delivering siRNA. The excellent response of siRNAs has impelled many organizations to market gene specificpre-designed kits to help researchers. About 3-5 siRNAsper gene are needed to have a potent RNAi effect . The consequent dollar intensive nature of this technology dissuades many laboratories from exploiting its true potential. Efforts are on to develop innovative yet reasonably affordable in vitro generation of siRNAs.

siRNA helps scientists to knockdown expressions of a target gene. This is done to have a superior understanding about the functions of the knocked down genes. They help understand the complexpathways genes that eventually will help develop effective treatments for many lethal diseases including cancer, autoimmune discrepancy, viral infections, Huntington disease and degenerative conditions. Without doubt, laboratory application of siRNA for its therapeutic uses is lately gaining popularity.

http://www.sirnatransfection.org/pages/sirna-transfection

Video animation: RNA interference

http://www.nature.com/nrg/multimedia/rnai/animation/index.html