Readings

Course readings.
WEEK #	TOPICS	READINGS
1	Welcome and Overview See the Lecture Summary	no readings
2	Introduction to RNAi See the Lecture Summary	Paper 1 Fire, A., S. Xu, M. K. Montgomery, S. A. Kostas, S. E. Driver, and C. C. Mello. "Potent and Specific Genetic Interference by Double-Stranded RNA in Caenorhabditis Elegans." Nature 391 (1998): 806-811. Paper 2 Winston, W. M., C. Molodowitch, and C. P. Hunter. "Systemic RNAi in C. elegans Requires the Putative Transmembrane Protein SID-1." Science 295 (2002): 2456-2459.
3	Hints of the Future: The Discovery of miRNAs See the Lecture Summary	Paper 1 Lee, R. C., R. L. Feinbaum, and V. A. Ambros. "The C. elegans Heterochronic Gene lin-4 Encodes Small RNAs with Antisense Complementarity to lin-14." Cell 75 (1993): 843-854. Paper 2 Lai, E. C. "Micro RNAs are Complementary to 3' UTR Sequence Motifs that Mediate Negative Post-Transcriptional Regulation." Nature Genetics 30 (2002): 363-364.
4	Mechanisms: Dicing and Slicing See the Lecture Summary	Paper 1 MacRae, I. J., K. Zhou, F. Li, A. Repic, A. N. Brooks, W. Z. Cande, P. D. Adams, and J. A. Doudna. "Structural Determinants of RNA Recognition and cleavage by Dicer." Nature Structural and Molecular Biology 14 (2007): 934-940. Paper 2 Wang, Y., S. Juranek, H. Li, G. Sheng, T. Tuschl, and D. J. Patel. "Structure of an Argonaute Silencing Complex with a Seed-Containing Guide DNA and Target RNA Duplex." Nature 456 (2008): 921-926.
5	How miRNAs Relate to siRNAs See the Lecture Summary	Paper 1 Doench, J. G., C. P. Petersen, and P. A. Sharp. "siRNAs Can Function as MiRNAs." Genes & Development 17 (2003): 438-442. Paper 2 Meister, G., M. Landthaler, A. Patkaniowska, Y. Dorsett, G. Teng, and T. Tuschl. "Human Argonaute2 Mediates RNA Cleavage Targeted by MiRNAs and siRNAs." Molecular Cell 15 (2004): 185-197.
6	RNAi in the Lab I: shRNA, siRNA, and miRNA Mimics See the Lecture Summary	Paper 1 Elbashir, S. M., J. Harborth, W. Lendeckel, A. Yalcin, K. Weber, and T. Tuschl. "Duplexes of 21-Nucleotide RNAs Mediate RNA Interference in Cultured Mammalian Cells." Nature 411 (2001): 494-498. Paper 2 Brummelkamp, T. R., R. Bernards, and R. Agami. "A System for Stable Expression of Short Interfering RNAs in Mammalian Cells." Science 296 (2002): 550-553.
7	RNAi in the Lab II: Screening for Hits See the Lecture Summary	Paper 1 Silva, J. M., K. Marran, J. S. Parker, J. Silva, M. Golding, M. R. Schlabach, S. J. Elledge, G. J. Hannon, and K. Chang. "Profiling Essential Genes in Human Mammary Cells by Multiplex RNAi Screening." Science 319 (2008): 617-620. Paper 2 Hu, G., J. Kim, Q. Xu, Y. Leng, S. H. Orkin, and S. J. Elledge. "A Genome-Wide RNAi Screen Identifies a New Transcriptional Module Required for Self-Renewal." Genes & Development 23 (2009): 837-848.
8	Company Visit: Alnylam See the Lecture Summary	no readings
9	RNAi Therapeutics I: Selecting Targets See the Lecture Summary	Paper 1 Jackson, A. L., S. R. Bartz, J. Schelter, S. V. Kobayashi, J. Burchard, M. Mao, B. Li, G. Cavet, and P. S. Linsley. "Expression Profiling Reveals off-Target Gene Regulation by RNAi." Nature Biotechnology 21 (2003): 635-637. Paper 2 Chen, P. Y., L. Weinmann, D. Gaidatzis, Y. Pei, M. Zavolan, T. Tuschl, and G. Meister. "Strand-Specific 5'-O-Methylation of siRNA Duplexes Controls Guide Strand Selection and Targeting Specificity." RNA 14 (2007): 263-274.
10	RNAi Therapeutics II: The Importance of Chemistry See the Lecture Summary	Paper 1 Czauderna, F., M. Fechtner, S. Dames, H. Aygün, A. Klippel, G. J. Pronk, K. Giese, and J. Kaufmann. "Structural Variations and Stabilising Modifications of Synthetic siRNAs in Mammalian Cells." Nucleic Acids Research 31 (2003): 2705-2716. Paper 2 Bramsen, J. B., et al. "A Large-Scale Chemical Modification Screen Identifies Design Rules to Generate siRNAs with High Activity, High Stability and Low Toxicity." Nucleic Acids Research 37 (2009): 2867-2881.
11	RNAi Therapeutics III: Efficacy in Animals See the Lecture Summary	Paper 1 McCaffrey, A. P., L. Meuse, T. T. Pham, D. S. Conklin, G. J. Hannon, and M. A. Kay. "RNA Interference in Adult Mice." Nature 418 (2002): 38-39. Paper 2 Soutschek, J., et al. "Therapeutic Silencing of An Endogenous Gene by Systemic Administration of Modified siRNAs." Nature 432 (2004): 173-178.
12	RNAi Therapeutics IV: Safety First See the Lecture Summary	Paper 1 Grimm, D., K. L. Streetz, C. L. Jopling, T. A. Storm, K. Pandey, C. R. Davis, P. Marion, F. Salazar, and M. A. Kay. "Fatality in Mice Due to Oversaturation of Cellular microRNA/Short Hairpin RNA Pathways." Nature 441 (2006): 537-541. Paper 2 John, M., et al. "Effective RNAi-Mediated Gene Silencing Without Interruption of the Endogenous microRNA Pathway." Nature 449 (2007): 745-747.
13	RNAi Therapeutics V: Delivery, Delivery, Delivery See the Lecture Summary	Paper 1 Hu-Lieskovan, S., J. D. Heidel, D. W. Bartlett, M. E. Davis, and T. J. Triche. "Sequence-Specific Knockdown of EWS-FLI1 by Targeted, Nonviral Delivery of Small Interfering RNA Inhibits Tumor Growth in a Murine Model of Metastatic Ewing's Sarcoma." Cancer Research 65 (2005): 8984-8992. Paper 2 Wolfrum, C., et al. "Mechanisms and Optimization of in vivo Delivery of Lipophilic siRNAs." Nature Biotechnology 25 (2007): 1149-1157.
14	Oral Presentations See the Lecture Summary	no readings