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NIH Solicits Proposals for RNAi Studies On Drug Addiction, Clinical Cancer Care

The National Institutes of Health this month announced that it has begun accepting applications for grant proposals focused on using genomic research tools, including RNAi-based technologies, to advance research examining the link between genetics and drug addiction.
“Genetic and genomic studies have identified genes and gene variants that potentially modulate the fundamental biological mechanisms underpinning addictive processes,” the NIH said. However, “discovery of these genes/variants, while extremely valuable, is only a first step in understanding molecular mechanisms of addiction.”
As such, the NIH will begin accepting research project applications focused on validating genes and gene variants associated with drug addiction, in addition to elucidating related molecular pathways and processes.
The NIH also this month re-issued a call for research applications for projects investigating the use of cellular, molecular, and genomic technologies such as RNAi in cancer care.
This funding opportunity announcement “specifically encourages research on commercially available [cellular, molecular, and genomic] clinical tools already in use, as well as experimental tools in the later stages of development and/or the regulatory approval pipeline,” according to the NIH.
Both funding opportunities officially open on Jan. 5. The NIH said that the size and number of awards issued will depend on the availability of funds and the submission of a sufficient number of meritorious applications.
RNAi and Drugs of Abuse
“Addiction to, or dependence on, drugs of abuse … is a major public health and economic problem,” the NIH said its announcement of the first funding opportunity. “Candidate genes/variants that play a role in addictive processes have been identified … and are priority targets for functional validation.”
Although the ideal functional validation would involve demonstrating the effect of a candidate gene or variant on a human phenotype relevant to addiction, “some human functional validation studies may not be feasible or ethical, necessitating the use of in vivo animal models or in vitro strategies,” the agency noted.
A number of public and private resources exist to facilitate this kind of functional validation, including C. elegans and other model organism mutants, embryonic stem cells for the generation of knockout animals, and reagents for RNAi-mediated silencing of candidate genes.
“As there are many scientific resources available, applications requesting funds to generate … resources that are already available must provide compelling justification to be competitive,” the NIH noted.

“RNAi depletion of candidate genes in cells, tissues, brain regions, or whole organisms can be used to identify phenotypes … [which] could range from the cellular — i.e. changes in morphology or function of synapses, dendritic spines, or neurons — to the organismal — i.e. changes in behavioral responses to drugs.”

The NIH said it will accept grant applications of varying depth and breadth, including ones investigating a single high-priority gene in detail or ones evaluating several hundred genes rapidly using high-throughput RNAi screening, for example.
“RNAi depletion of candidate genes in cells, tissues, brain regions, or whole organisms can be used to identify phenotypes … [which] could range from the cellular — i.e., changes in morphology or function of synapses, dendritic spines, or neurons — to the organismal — i.e., changes in behavioral responses to drugs,” the NIH noted.
The NIH also said that projects linking drug abuse-related function to genes or variants in non-coding RNA, microRNA, or other putative non-protein coding regions of the genome are appropriate under the funding opportunity.
The full text of the funding opportunity can be found here.
RNAi in Cancer Care
“To date, cancer research in the emerging field of molecular medicine has primarily focused on the discovery of novel biomarkers and therapeutic targets, and the development of innovative biotechnologies to improve cancer prevention, early detection, diagnosis, and treatment,” the NIH said in the re-issued funding opportunity announcement. “With many of these technologies still in experimental phases, minimal attention has been paid to their likely and measured effects on healthcare delivery.”
As such, the NIH said it is soliciting grant applications for projects to improve the understanding of access, quality, and costs associated with using cellular, molecular, and genomic technologies in cancer care.
“With the steady increase in the number and diversity of emerging [cellular, molecular, and genomic] technologies that are commercially available or in the developmental pipeline, a systematic approach is needed to evaluate their utilization, distribution, and impact on cancer care delivery,” the agency said.
Two examples of the kind of cellular, molecular, and genomic technology that is relevant to the funding opportunity are RNAi-based therapies for cancer and nanoparticle-based drug-delivery systems, the NIH noted.
A number of companies within the RNAi space are developing one or both, including Alnylam Pharmaceuticals (see RNAi News, 11/8/2007), Kylin Therapeutics (see RNAi News, 7/19/2007), Silence Therapeutics (see RNAi News, 5/3/2007), Intradigm (see RNAi News, 10/18/2007), and Calando Pharmaceuticals (see RNAi News, 3/22/2007).
“By engaging in both the fields of molecular medicine and applied cancer research, an interdisciplinary knowledge base can be created to help reduce the burden of cancer for patients, their families, institutions, and communities,” the NIH said.
The full text of the funding opportunity can be found here.

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