Design of microRNA therapeutics
Presenter: Andrea Kasinski, Purdue University, USA
Date: May 15, 2019
Description:
MicroRNAs (miRNAs) have emerged as powerful regulators of the genome and, through concerted efforts to identify their function and evaluate their ability to alter cell growth in vitro and in vivo, some have gained favor as potential therapeutics. Although these miRNA-based approaches can revolutionize the way that diseases are diagnosed and treated, there are multiple considerations and challenges that one must consider when embarking on a miRNA-based therapeutics approach. This webinar will breakdown the basic steps needed for designing a miRNA therapeutic. Topics will range from selecting an appropriate miRNA candidate to identifying a suitable delivery platform to achieve safe and robust targeting. Both miRNA overexpression and miRNA sequestration approaches will be discussed including backbone modifications that are being made to the miRNA, or sequestering agent that can improve stability, and thus reduce in vivo dosing.
Recording of the Webinar: Click Play to View
In addition, Prof. Kasinski would like to make the slides available for download: Kasinski OTS webinar
Presenter Biography
Andrea Kasinski, Purdue University, USA
Andrea Kasinski, PhD, is the William and Patty Miller Assistant Professor of Biological Sciences at Purdue University. After finishing her PhD with Dr. Haian Fu at Emory University, Dr. Kasinski worked as a Post-Doc with Prof. Frank J. Slack at Yale University.
Her laboratory focuses on identifying biologically important RNAs whose misexpression drives the tumorigenic process and utilizes this information to design, develop, and implement RNA-based therapeutics. She showed therapeutic benefit for both lentiviral- and systemically delivered miR-34 in multiple murine cancer models. These studies were instrumental in advancing the first miRNA therapeutic MRX34, into clinical trials.
Dr. Kasinski is also involved in developing and testing novel small RNA delivery platforms. In collaboration with Dr. Philip Low, she developed FolamiRs – folate-conjugated microRNAs for vehicle-free delivery.
References
- MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy.
Kasinski AL, Slack FJ.
Nat Rev Cancer. 2011 Nov 24;11(12):849-64. - miRNA-34 prevents cancer initiation and progression in a therapeutically resistant K-ras and p53-induced mouse model of lung adenocarcinoma.Kasinski AL, Slack FJ.
Cancer Res. 2012 Nov 1;72(21):5576-87. - Discovering the first microRNA-targeted drug.
Lindow M, Kauppinen S.
J Cell Biol. 2012 Oct 29;199(3):407-12. - A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer.
Kasinski AL, Kelnar K, Stahlhut C, Orellana E, Zhao J, Shimer E, Dysart S, Chen X, Bader AG, Slack FJ.
Oncogene. 2015 Jul;34(27):3547-55. - MicroRNAs in Cancer: A Historical Perspective on the Path from Discovery to Therapy.
Orellana EA, Kasinski AL.
Cancers (Basel). 2015 Jul 27;7(3):1388-405. - Principles in the design of ligand-targeted cancer therapeutics and imaging agents.
Srinivasarao M, Galliford CV, Low PS.
Nat Rev Drug Discov. 2015 Mar;14(3):203-19. - FolamiRs: Ligand-targeted, vehicle-free delivery of microRNAs for the treatment of cancer.
Orellana EA, Tenneti S, Rangasamy L, Lyle LT, Low PS, Kasinski AL.
Sci Transl Med. 2017 Aug 2;9(401). - Enhancing MicroRNA Activity through Increased Endosomal Release Mediated by Nigericin.
Orellana EA, Abdelaal AM, Rangasamy L, Tenneti S, Myoung S, Low PS, Kasinski AL.
Mol Ther Nucleic Acids. 2019 Apr 11;16:505-518.
