Course Meeting Times
Lectures: 1 session / week, 2 hours / session
At least one of the following courses:
7.05 General Biochemistry
7.06 Cell Biology
7.28 Molecular Biology
The ultimate goal of medicine is to cure disease, yet, despite centuries of effort, modern medicine struggles against the same obstacles today as it did in its early days: finding the source of the disease and treating it specifically without side effects. Even with significant advances in medicinal chemistry over many decades, traditional small molecule therapeutics remain unpredictable because of a lack of specificity. Similarly, the recent advent of recombinant DNA technology, while ushering in an era of protein-based therapeutics, has achieved only limited success because of difficulties posed by the large sizes of these macromolecules. What, then, is the next therapeutic frontier? The answer may lie in RNA interference (RNAi), a fundamental biological process discovered less than a decade ago and recognized soon afterwards with the 2006 Nobel Prize in Physiology or Medicine. RNAi is mediated by small interfering RNAs (siRNAs), which direct the efficient degradation of specific messenger RNAs, thereby inhibiting protein synthesis. Since its discovery, the use of RNAi has revolutionized basic science research by allowing dissection of cellular processes with unprecedented specificity. In addition, the ability to correlate the silencing of individual gene products with phenotypes allows scientists to identify the genetic sources and pathways of disease. More importantly, the race is now on to develop siRNAs as therapeutic agents and achieve a level of efficacy that has eluded medicine thus far. In this course, we will focus on the therapeutic potential of RNAi. Specifically, we will discuss its discovery, functions in normal biological processes, utility as an experimental tool, potential for therapeutic use, and pursuit by the biotechnology industry.
The main objectives of this course are to introduce students to the primary scientific literature and the process of finding/reading research papers as well as to expose students to the important emerging field of RNA interference. In the process of reading the assigned publications, you will learn how to analyze papers to extract key points and to examine scientific papers critically. Our focus will be on papers that have made significant conceptual contributions to RNA interference. Students will be exposed to both basic and applied biology, learning about a critical pathway that is being harnessed potentially to revolutionize medicine.
During each session, we will discuss two scientific articles, with emphasis placed on the principles of experimental design, the use of control experiments, the details of experimental methodology, and the interpretation of experimental data. At the end of each session, the instructors will present a 15-minute introduction to the topic of the following week's assigned reading.
The course is graded pass/fail. A passing grade will be awarded to students who have satisfactory attendance, participate in discussions and have completed class assignments appropriately.
||Welcome and Overview
||Introduction to RNAi
||Hints of the Future: The Discovery of miRNAs
||Mechanisms: Dicing and Slicing
||How miRNAs Relate to siRNAs
||RNAi in the Lab I: shRNA, siRNA, and miRNA Mimics
||RNAi in the Lab II: Screening for Hits
||Company Visit: Alnylam
||RNAi Therapeutics I: Selecting Targets
||RNAi Therapeutics II: The Importance of Chemistry
||RNAi Therapeutics III: Efficacy in Animals
||RNAi Therapeutics IV: Safety First
||RNAi Therapeutics V: Delivery, Delivery, Delivery