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Cellular Delivery of RNA Nanoparticles Lorena Parlea, Anu Puri, Wojciech K

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Cellular Delivery of RNA Nanoparticles Lorena Parlea, Anu Puri, Wojciech K Subscriber access provided by Northern Illinois University Review Cellular Delivery of RNA Nanoparticles Lorena Parlea, Anu Puri, Wojciech K. Kasprzak, Eckart Bindewald, Paul Zakrevsky, Emily Satterwhite, Kenya Joseph, Kirill A Afonin, and Bruce A Shapiro ACS Comb. Sci., Just Accepted Manuscript • DOI: 10.1021/acscombsci.6b00073 • Publication Date (Web): 10 Aug 2016 Downloaded from http://pubs.acs.org on August 21, 2016 Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts. ACS Combinatorial Science is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties. Page 1 of 81 ACS Combinatorial Science 1 2 3 Cellular Delivery of RNA Nanoparticles 4 5 6 7 8 Lorena Parlea a, Anu Puri a, Wojciech Kasprzak b, Eckart Bindewald b, Paul Zakrevsky a, Emily 9 10 c c c,d a* 11 Satterwhite , Kenya Joseph , Kirill A. Afonin and Bruce A. Shapiro 12 13 14 a 15 Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, Frederick, MD, 16 17 18 21702, USA 19 20 b Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer 21 22 Research, Frederick, MD 21702, USA 23 24 c 25 Department of Chemistry, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, 26 27 USA 28 29 d Nanoscale Science Program, University of North Carolina at Charlotte, Charlotte NC 28223, USA; The 30 31 32 Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte 33 34 NC 28223, USA. 35 36 37 38 39 * To whom correspondence should be addressed ( [email protected] ) 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 ACS Paragon Plus Environment ACS Combinatorial Science Page 2 of 81 1 2 3 Keywords : RNA, self-assembly, Nanoconstruct, RNA Nanoparticle, Therapeutics, Delivery 4 5 6 7 8 Abbreviations: 9 10 11 3D – three dimensional, kDA – kiloDalton, MD – molecular dynamics, NP – nanoparticles, nt – 12 13 nucleotide, OEL – Oxime ether lipids, polyethylenglycol – PEG, miRNA- micro-RNA, piRNA – piwi- 14 15 RNA, siRNA – small interfering RNA, RNAi – RNA interference, DS RNA – Dices substrate RNA, 16 17 18 RISC – RNA-induced Silencing Complex 19 20 21 22 Table of Contents 23 24 25 26 27 Keywords ................................................................................................................................................................................................... 2 28 29 Abstract ....................................................................................................................................................................................................... 4 30 Introduction ............................................................................................................................................................................................... 5 31 32 Functional RNAs ..................................................................................................................................................................................... 5 33 34 Interfering RNAs ................................................................................................................................................................................ 5 35 Aptamers ................................................................................................................................................................................................ 8 36 37 Splicing Modulators .......................................................................................................................................................................... 9 38 39 RNA Switches ...................................................................................................................................................................................... 9 40 Ribozymes ............................................................................................................................................................................................. 9 41 42 Exogenous mRNAs .......................................................................................................................................................................... 10 43 44 CRISPR RNAs ................................................................................................................................................................................... 10 45 46 RNA/DNA hybrids ........................................................................................................................................................................... 11 47 Rational RNA Nanostructure Design ........................................................................................................................................... 11 48 49 Manual design of RNA Nanostructures based on naturally occurring RNA 3D motifs .................................... 13 50 51 Computational design of RNA Nanostructures using naturally occurring RNA 3D motifs ............................ 14 52 3-D Motif-based nanostructures ........................................................................................................................................... 14 53 54 De-novo Design of RNA Scaffolds ........................................................................................................................................ 16 55 56 Functionalization of RNA Nanostructures ............................................................................................................................ 17 57 Hybrid technology in RNA NPs ................................................................................................................................................. 18 58 59 60 2 ACS Paragon Plus Environment Page 3 of 81 ACS Combinatorial Science 1 2 3 Challenges in delivering RNAs ........................................................................................................................................................ 20 4 5 Degradation ........................................................................................................................................................................................ 21 6 7 Stability in blood ............................................................................................................................................................................... 22 8 Hepato-Renal Clearance ............................................................................................................................................................... 22 9 10 Toxicity and Immunogenicity ..................................................................................................................................................... 23 11 12 Cellular Uptake ................................................................................................................................................................................. 24 13 14 Endosomal Escape ........................................................................................................................................................................... 26 15 Off-target Effects .............................................................................................................................................................................. 26 16 17 Delivery methods for RNA therapeutics and RNA NPs ....................................................................................................... 26 18 19 “Naked” Delivery ............................................................................................................................................................................. 27 20 Mediated Delivery ............................................................................................................................................................................ 28 21 22 Polymers .........................................................................................................................................................................................
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