SOLICITATION NOTICE
B -- Provide validated shRNA constructs to the NCI's Integrative Cancer Biology Program (ICBP) Community
- Notice Date
- 7/24/2006
- Notice Type
- Solicitation Notice
- NAICS
- 541990
— All Other Professional, Scientific, and Technical Services
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Bldg 427, Room 12, Frederick, MD, 21702
- ZIP Code
- 21702
- Solicitation Number
- RFPS06-182
- Response Due
- 8/4/2006
- Archive Date
- 8/19/2006
- Description
- Advances in genomics have led to the identification of hundreds of genes that have the potential for improving our understanding and management of cancer. These genes have been identified primarily by alterations in their expression detected by experimental approaches including large scale mutation analysis or expression array analysis. While these data often provide a useful starting point, information about a gene?s function leads to a better understanding of its role in the normal cell and in the cancer process and should lead to more effective biomarker identification and the design of therapeutics. Functional analysis of genes has traditionally been tedious and time-consuming. Biological assessment is usually performed by carefully manipulating the gene of interest either in vitro or in vivo and observing phenotypic changes. These experiments are relatively quick in cell lines and lower model organisms such as C. elegans or S. cerevisiea; however in higher animal models, like mice, the protocols are time consuming and involve sophisticated gene transfer and subsequent breeding. RNA interference (RNAi) and microRNA (miRNA) are evolutionarily ancient mechanisms to regulate gene expression that have recently been discovered and exploited in a broad range of organisms as a fast and efficient methodology for functional genetics. There are two basic methods for the use of noncoding RNA for gene?specific inhibition of transcription or translation: 1) cytoplasmic delivery of short dsRNA oligonucleotides (siRNA), which mimic an active intermediate of an endogenous RNAi mechanism and 2) nuclear delivery of gene expression cassettes that express a short hairpin RNA (shRNA), which mimic the interfering miRNA active intermediate of a different endogenous RNAi mechanism. Both of these have proven effective in experimental settings and have specific strengths and weaknesses (Nature Biotechnology 23, 227 ? 231, 2004). Success of the RNAi technology in tissue culture and animals has been dependent on delivery systems for transporting the RNA or construct into the cell of interest. Non-viral gene delivery systems are a diverse collection of technologies that are applicable to both of these forms of RNAi. Viral delivery systems efficiently transfer the RNAi into cells either transiently or for stable production. Viral vectors also allow the use of the more efficient shRNA. The technology has already revolutionized functional genomic studies, however, there is variation of inhibition which is dependent on the specific sequences within each targeted gene, and in some instances the cell type. While much of this functional variation of RNAi constructs is sequence related, the biological mechanism of these effects is not understood sufficiently to predict success, failure or partial effect. Therefore, in order for these reagents to be broadly used tools, RNAi expression systems and formats need extensive verification of biological activity, i.e. ability of the particular RNAi constructs to specifically down-regulate or eliminate protein?s expression. Many RNAi constructs and RNAi libraries have been generated to date. They have proven useful in the identification of new oncogenes and tumor suppressor genes. In addition, these molecules can be used to functionally confirm the importance or impact of specific genes or proteins in the carcinogenic process (Willingham et al. (2004) RNAi and HTS exploring cancer through systematic loss of function, Oncogene 23:8392; Hannon & Rossi (2004) Unlocking the potential of the human genome with RNA interference, Nature 431:371). This functional knowledge is not only important in the identification of potential biomarkers and therapeutic targets but provides the initial insight into the overall design of normal and cancer cells. The Integrative Cancer Biology Program (ICBP) of the National Cancer Institute is a consortium of research centers utilizing a systems biology approach to understanding cancer processes. The centers use both experimental and mathematical approaches to develop computational models of cancer processes. These centers focus on specific cancers and mechanisms, such as signaling pathways and tumor migration. As a group they have identified areas of common interest and common need. The NCI?s ICBP has identified RNAi technology and resources as one of the critical tools to facilitate both their research and that of the broader cancer research community. With consultation of the ICBP investigators, the NCI staff has determined that a library of validated RNAi resources would benefit NCI cancer research efforts. This library would initially consist of shRNAs targeted to genes chosen collectively by the ICBP investigators and deemed important in cancer research. This request for proposals is to obtain and evaluate shRNA lentiviral vector expression constructs for 134 human genes selected by the NCI. Preference is for the Hannon lentiviral library (http://cgap.nci.nih.gov/RNAi ) however if a sufficient number of constructs for each gene are unavailable in that library, the RNAi Consortium (TRC) http://www.broad.mit.edu/genome_bio/trc/rnai.html) library may act as a source for constructs to be evaluated. This contract will cover the biological testing of those constructs, the posting of the evaluation data, and the distribution or appropriate transfer of the material.
- Record
- SN01096157-W 20060726/060724220317 (fbodaily.com)
- Source
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