title: Modulation of Gene Expression by Polymer Nanocapsule Delivery of DNA Cassettes Encoding Small RNAs.
abstract: Small RNAs, including siRNAs, gRNAs and miRNAs, modulate gene expression and serve as potential therapies for human diseases. Delivery to target cells remains the fundamental limitation for use of these RNAs in humans. To address this challenge, we have developed a nanocapsule delivery technology that encapsulates small DNA molecules encoding RNAs into a small (30 nm) polymer nanocapsule. For proof of concept, we transduced DNA expression cassettes for three small RNAs. In one application, the DNA cassette encodes an shRNA transcriptional unit that downregulates CCR5 and protects from HIV-1 infection. The DNA cassette nanocapsules were further engineered for timed release of the DNA cargo for prolonged knockdown of CCR5. Secondly, the nanocapsules provide an efficient means for delivery of gRNAs in the CRISPR/Cas9 system to mutate integrated HIV-1. Finally, delivery of microRNA-125b to mobilized human CD34+ cells enhances survival and expansion of the CD34+ cells in culture.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America; California NanoSystems Institute (CNSI), University of California Los Angeles, Los Angeles, California, United States of America; University of California Los Angeles AIDS Institute, Los Angeles, California, United States of America.
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America; University of California Los Angeles AIDS Institute, Los Angeles, California, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.affiliation: Department of Biomolecular and Chemical Engineering, University of California Los Angeles, Los Angeles, California, United States of America; California NanoSystems Institute (CNSI), University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Division of Hematology-Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America; University of California Los Angeles AIDS Institute, Los Angeles, California, United States of America.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kamata
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America; University of California Los Angeles AIDS Institute, Los Angeles, California, United States of America.
authors.forename: Irvin S Y
authors.initials: IS
authors.lastname: Chen
mesh_terms: D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D015658:HIV Infections / Q000235:genetics / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000821:virology; D035683:MicroRNAs / Q000235:genetics; D053769:Nanocapsules / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry*; D017393:RNA Editing / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D019713:Receptors, CCR5 / Q000737:chemistry* / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D053769:Nanocapsules; D011108:Polymers; D034741:RNA, Small Interfering; D019713:Receptors, CCR5; D004247:DNA