Gene Therapy Breakthrough- Three Micro RNA inhibition injections reduces cholesterol 30%, 2013 for human use

Two forms of RNA either boost or suppress protein production, and scientists have in recent years discovered this system is central to a range of illnesses, including cancers, viral infections, cardiovascular disease and neurological disorders.

Previous attempts to manipulate this process have failed because the drug molecules used were too large to get to the target cells. Now scientists at Santaris Pharma have developed smaller compounds that can cross cell membranes and intercept the microRNA molecules that usually put a brake on protein production.

LNA-mediated microRNA silencing in non-human primates.

MicroRNAs (miRNAs) are small regulatory RNAs that are important in development and disease and therefore represent a potential new class of targets for therapeutic intervention. Despite recent progress in silencing of miRNAs in rodents, the development of effective and safe approaches for sequence-specific antagonism of miRNAs in vivo remains a significant scientific and therapeutic challenge. Moreover, there are no reports of miRNA antagonism in primates. Here we show that the simple systemic delivery of a unconjugated, PBS-formulated locked-nucleic-acid-modified oligonucleotide (LNA-antimiR) effectively antagonizes the liver-expressed miR-122 in non-human primates. Acute administration by intravenous injections of 3 or 10 mg kg-1 LNA-antimiR to African green monkeys resulted in uptake of the LNA-antimiR in the cytoplasm of primate hepatocytes and formation of stable heteroduplexes between the LNA-antimiR and miR-122. This was accompanied by depletion of mature miR-122 and dose-dependent lowering of plasma cholesterol. Efficient silencing of miR-122 was achieved in primates by three doses of 10 mg kg-1 LNA-antimiR, leading to a long-lasting and reversible decrease in total plasma cholesterol without any evidence for LNA-associated toxicities or histopathological changes in the study animals. Our findings demonstrate the utility of systemically administered LNA-antimiRs in exploring miRNA function in rodents and primates, and support the potential of these compounds as a new class of therapeutics for disease-associated miRNAs.

Mice on a high fat diet were given three injections of a drug to block miRNA-122, a compound in the liver that controls cholesterol levels. Those given the highest dose had 30 per cent lower cholesterol levels than those given placebo injections, and the effects lasted three weeks after the last injection.

Laboratory tests also showed that blocking miRNA-122 also prevented the hepatitis C virus replicating. Human trails of a drug to treat hepatitis C will begin next year and scientists are using the method to develop a treatment to combat blood cancers.

Santaris predicts new therapies will be ready for use by patients within five years if trials go well.

Santaris Pharma is preparing to advance its first LNA-antimiR compound, targeting miR-122, into human clinical testing in the first half of 2008.

Safer and more precise methods of targeting gene therapy are being made with synthetic zinc fingers.

Researchers have figured out the real problem with a common gene therapy delivery system the adenovirus type 5. Adenovirus consists of three major proteins – fiber, penton and hexon. Previously researchers thought the fiber protein was the problem. New research indicates it is the hexon. Now by modifying the hexon they can make adenovirus delivered gene therapy safe.

“Now that we have learned the mechanism that an adenovirus uses we could modify that process by genetically engineering the virus, to improve uptake into several cell types, including stem cells,” says Dr. Napoli.

There has also been progress in using gene therapy to treat brain cancer.

Safe and effective gene therapy or drugs that safely target genetic effects could be used to safely boost muscle mass by four times. This could make people stronger and healthier. Better weight control with more muscle that burns excess fat. 2012-2016 seems to be the likely timeframe when these procedures start making a big societal impact. It could happen sooner and more could happen later, but that seems to be the time when more people will realize that a new age is upon the world.

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