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NIH Challenge Grants Offer Opportunities for RNAi, microRNA Researchers

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The National Institutes of Health this month announced that it has earmarked at least $200 million to fund grant projects, including ones involving RNAi and microRNAs, over the next two years as part of a bid to support biomedical research in the United States.

The funding comes courtesy of the $787 billion stimulus package recently signed into law by President Obama, which increased financing to a variety of governmental health and research agencies, including the NIH and the US Food and Drug Administration.

The initiative, called NIH Challenge Grants in Health and Science Research, will "support research on topic areas [addressing] specific scientific and health research challenges in biomedical and behavioral research that would benefit from significant two-year jumpstart funds," the NIH said.

As part of this effort, the NIH said that it expects to finance research projects on so-called Challenge Topics, which are directed towards "specific knowledge gaps, scientific opportunities, new technologies, data generation, or research methods that would benefit from an influx of funds to quickly advance the area in significant ways."

According to the NIH, Challenge Grant funding will be available for up to two years, beginning in fiscal 2009, which started on Oct. 1, 2008, and running through fiscal 2010, which begins on Oct. 1. The agency expects to award 200 or more grants, which are each eligible for as much as $1 million in total costs, depending on the number of "scientifically meritorious applications" received.

In line with the goal of President Obama's stimulus package, "in particular, to preserve and create jobs and promote economic recovery in the United States, and to provide investments needed to increase economic efficiency by spurring technological advances in science and health," the NIH noted that grant applicants must be domestic institutions or organizations.

Among the Challenge Topics highlighted by the NIH are four specifically focused on advancing RNAi- and miRNA-based technologies, including one involving the translation of gene-silencing technologies into therapeutics through monkey and large-animal studies.

Technologies such as antisense and RNAi "have been rapidly developed and refined in cell culture and rodent models of disease," while RNAi strategies now include the use of "viral vectors to deliver and continually express the gene-silencing construct," the NIH said.

"To realize the potential of these technologies, however, experiments in non-human primates or appropriate large animal models are necessary to determine the feasibility of this therapeutic approach for the treatment of chronic neurological/mental health diseases with either focal or diffuse pathologies," the agency noted.

Another Challenge Area for which the agency is accepting research proposals under the initiative is the study of miRNAs in cancer. Having been shown to be "ubiquitous in the mammalian genome [while] exerting control over many cancer genes and processes," the NIH is seeking research proposals related to the development of "new technologies and informatics tools [that] are needed to survey the microRNAs in cancer and their role in its development."

Under the Challenge Grant initiative, the NIH is also on the lookout for projects investigating the role of miRNAs and other non-coding RNAs in pre-neoplastic lesions and their usefulness in predicting progression to cancer and early cancer detection.

The agency also recognizes the therapeutic potential of non-coding RNAs, and will consider grant proposals related to the development of miRNA-based therapeutic strategies for heart, lung, and blood diseases.

Currently, miRNAs are believed to "play significant roles" in endothelial cell migration and proliferation, and vascular and airway inflammation, fibrosis, and remodeling, "all of which are key mechanisms in atherosclerosis … thrombosis, and chronic lung disease," the NIH said. Still, "research is needed to improve our understanding of the miRNA network and its function related to heart, lung, and blood diseases, and to develop new targets and therapeutic strategies … to treat them."

Other Opportunities

Under the NIH Challenge Grants in Health and Science Research initiative, the agency is also seeking proposals for projects that, while not specifically involving RNAi, could include aspects of the technology.

One of these relates to the use of gene-silencing strategies for oral and craniofacial disorders.

"The application of oligonucleotide-based methods for modifying gene expression has emerged as a powerful research tool [with] … vast potential for understanding disease processes and for the development of new therapeutics," the NIH noted.

In light of this, the agency is requesting proposals for projects focused on "harnessing oligonucleotide-based approaches such as RNA interference to modify the expression of genes associated with oral, dental, and craniofacial diseases and disorders, coupled with technological innovations to improve the efficiency of delivery, specificity, processing, or stability of the … strategy."

Meanwhile, the agency has also called for project proposals related improving transdermal drug-delivery technologies, including ones for RNAi-based therapeutics.

"Transdermal delivery of drugs for local and systemic therapy have several advantages over oral and [intravenous] administration, [as well as] hypodermic injection … [and] there is a need to improve our understanding of the skin barrier function and [to] identify molecules and processes that could be targeted to affect skin permeability," the NIH said.

Projects in the challenge area eligible for funding could include those extending transdermal delivery to macromolecules such as siRNAs, it added.

Grant proposals are due by April 27. Additional details about the initiative can be found here.

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