(Fast-Track proposals will be accepted.)
Number of anticipated awards: 3–5
Budget (total costs):
Phase I: $200,000 for 9 months;
Phase II: $1,000,000 for 2 years
It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded.
The deadline for receipt of all contract proposals submitted in response to this solicitation has expired. It was: November 13, 2012 by 5 p.m. EST.
In 2011, the SBIR Development Center hosted an industry roundtable to solicit inputs from life science industry professionals on emerging areas that are ripe for technology development by the small business community. Participants at this meeting expressed strong interest in using the SBIR mechanism to foster and encourage the development of novel RNA interference (RNAi) delivery platforms, particularly as a strategy for addressing therapeutic targets previously deemed "undruggable" by small molecules. Such therapeutics are gaining prominence due to their versatility and efficiency in treating cancer, as well as a variety of other genetic diseases; however, treating patients with RNAi has proven challenging, as it is difficult to achieve intracellular delivery to specific tissues and organs expressing the target gene. In particular, cellular uptake of naked RNAi is extremely inefficient owing to its polyanionic nature. The majority of intravenously administered RNAi is removed from circulation by hepatic and renal clearance, and the remaining RNAi is subject to degradation by nonspecific nucleases in the blood. Moreover, injecting large quantities of RNAi may elicit an immune response, and other "off-target" effects may result in toxicity. While RNAi delivery to tumor cells poses these and other challenges, the ability to overcome these challenges is expected to facilitate the development of new and highly efficacious anti-cancer agents. Nanoparticle-based delivery systems are especially attractive as such strategies afford the opportunity to target specific cell, tissue, and organ types, while also increasing circulation half-life and shielding RNAi from degradation. Importantly, ongoing clinical trials are successfully utilizing nanoparticle-based delivery systems for cancer-related RNAi therapeutics, indicating that nanotechnology-based approaches hold great promise. To accelerate such efforts, the National Cancer Institute (NCI) requests proposals for the development of novel, commercially viable nanotechnology-based platforms for the delivery of RNAi cancer therapeutics.
Proposals submitted under this contract topic should involve the design, fabrication, characterization, and preclinical evaluation of novel nanoparticle-based drug formulations capable of delivering candidate RNAi therapeutics for the treatment of cancer. Of particular interest are delivery systems that can achieve targeted delivery of RNAi to tumor cells, favorable pharmacokinetics and circulation times, and efficient uptake of RNAi by tumor cells. Nanotechnologies which minimize immune responses and/or off-target effects of RNAi are also desirable.
Nanotechnology-based RNAi therapeutic agents acceptable under this contract topic include siRNA, shRNA, miRNA, other ncRNA(s) and combinations thereof. Antisense oligonucleotides are also acceptable. This contract topic is not intended to fund basic research to identify molecular targets for RNAi therapy, conduct exhaustive comparative studies of multiple nanoparticle delivery systems, or establish new animal models. Concepts delivering DNA, messenger RNA, and/or proteins are also not acceptable candidates for this topic, nor are viral delivery platforms for RNAi.
The RNAi-nanoparticle constructs under development may incorporate additional functionalities to supplement or enhance the therapeutic RNAi. Such functionalities may include, but are not necessarily limited to, the following: