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MicroRNAs May Regulate 1/3 of Human Genome

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As the field of microRNA research expands, it is becoming increasingly clear that these small RNAs play a significant role in cellular regulation. But according to a letter to the editor in the Jan. 14 issue of Cell, that role may be bigger than some have thought.

According to the findings of David Bartel, a researcher at the Whitehead Institute, MIT scientist Christopher Burge, and Benjamin Lewis, a graduate student in both researchers’ labs, miRNAs may be responsible for regulating up to one-third of all human genes.

Researchers used a computer algorithm they designed, called TargetScan, to examine mRNAs from the human genome for sequences that would make them likely targets for miRNAs. They then looked to see if these sequences could be found in the corresponding genomes of the mouse, rat, dog, and chicken.

“What we find is actually quite a striking preservation of sequences corresponding to the 5’ end of the microRNAs, which we’ve called the seed,” Lewis says.

In the Cell paper, Bartel and his colleagues state that they began with the “UTRs corresponding to mRNAs annotated in the UC Santa Cruz Genome Browser database, and a set of 62 unique seed matches that represented 148 human miRNA genes and defined the families of known miRNAs conserved” in the genomes of the five species.

Lewis says, “It’s not that we’re just finding matches, it’s not just that we’re able to pair the mRNA to the microRNA or model that matching — we’re doing statistics on the probability of observing these matches relative to a background distribution that’s modeled with these control sequences. That’s been a really essential part of the work.”

— Doug Macron

PATENT WATCH

US Patent application 20050020525. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA). Assignee: Sirna Therapeutics. Inventors: James McSwiggen, Bharat Chowrira, Leonid Beigelman, Dennis Macejak, Shawn Zinnen, Pamela Pavco, Peter Haeberli, David Morissey, Kathy Fosnaugh, Sharon Jamison, Nassim Usman, James Thompson, Chandra Vargeese, Weimen Wang, Tonqian Chen, Narendra Vaish. Filed: January 14, 2004.

According to the abstract, this patent covers “synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid, short interfering RNA, double-stranded RNA, micro-RNA, and short hairpin RNA.” More generally, it involves “methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications.”

 

US Patent application 20050020521. In vivo gene silencing by chemically modified and stable siRNA. Assignee: University of Massachusetts. Inventor: Tariq Rana. Filed: September 25, 2003.

This patent covers methods of using RNAi, providing modified siRNAs that have better stability and target efficiency. “Modifications include chemical crosslinking between the two complementary strands of an siRNA and chemical modification of a 3’ terminus of a strand of an siRNA.”

Datapoint

$650 million

Projected value of the market for drug discovery based on RNAi for 2005, according to a report by Edward Weck from D&MD Publications. The same market is predicted to expand to $1 billion by 2010.

 

NIH will award grants to small business folks to help “develop new approaches and chemical modifications that will increase the long-term stability, delivery, and targeting of siRNAs in cells and tissues for laboratory and therapeutic applications,” according to the agency. Budgets of up to $100,000 per year may be requested for a maximum of two years for Phase I programs; budgets of up to $500,000 per year may be requested for a maximum of three years for Phase II programs.

 

CytRx signed an agreement to privately place about 17.3 million shares of common stock with institutional investors. Gross proceeds of the investment are expected to be about $21.3 million for the company. The financing will enable CytRx to embark on a phase 2 trial for its ALS treatment and expand other programs as well.

 

GeneGo signed a licensing deal with Japanese firm RNAi Co., allowing the RNAi company to use GeneGo’s MetaCore pathway analysis database and software for use in RNAi-based drug discovery efforts.

 

Dharmacon signed a deal to provide Genentech with various siRNA reagents, including Dharmacon’s Human Druggable Genome library. Financial terms of the deal were not disclosed.

 

Shifting to a focus on human therapeutics, Cambria Biosciences is looking for licensees for its RNAi-based pest management technology.

The Scan

WHO Seeks Booster Pause

According to CNN, the World Health Organization is calling for a moratorium on administering SARS-CoV-2 vaccine boosters until more of the world has received initial doses.

For Those Long Legs

With its genome sequence and subsequent RNAi analyses, researchers have examined the genes that give long legs to daddy longlegs, New Scientist says.

September Plans

The New York Times reports that the US Food and Drug Administration is aiming for early September for full approval of the Pfizer-BioNTech SARS-CoV-2 vaccine.

Nucleic Acids Research Papers on Targeting DNA Damage Response, TSMiner, VarSAn

In Nucleic Acids Research this week: genetic changes affecting DNA damage response inhibitor response, "time-series miner" approach, and more.