Bundling mRNA Strands to Prepare Nano-Assemblies with Enhanced Stability Towards RNase for In Vivo Delivery.

Nanostructures / chemistry Nucleic Acid Conformation RNA Stability RNA, Messenger / chemistry Ribonucleases / chemistry
RNA structure drug delivery gene technology mRNA ribonuclease

Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
12 08 2019
Historique:
received: 26 04 2019
revised: 28 05 2019
pubmed: 13 6 2019
medline: 22 9 2020
entrez: 13 6 2019
Statut: ppublish

Résumé

Ribonuclease (RNase)-mediated degradation of messenger RNA (mRNA) poses a huge obstruction to in vivo mRNA delivery. Herein, we propose a novel strategy to protect mRNA by structuring mRNA to prevent RNase attack through steric hinderance. Bundling of mRNA strands through hybridization of RNA oligonucleotide linkers allowed the preparation of mRNA nano-assemblies (R-NAs) comprised of 7.7 mRNA strands on average, mostly below 100 nm in diameter. R-NA formation boosted RNase stability by around 100-fold compared to naïve mRNA and preserved translational activity, allowing protein production. A mechanistic analysis suggests that an endogenous mRNA unwinding mechanism triggered by 5'-cap-dependent translation may induce selective R-NA dissociation intracellularly, leading to smooth translation. R-NAs showed efficient mRNA transfection in mouse brain, demonstrating the feasibility for in vivo administration.

Identifiants

DOI: 10.1002/anie.201905203 PMID: 31187576
pubmed: 31187576
doi: 10.1002/anie.201905203
doi:

Substances chimiques

RNA, Messenger 0
Ribonucleases EC 3.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

11360-11363

Subventions

Organisme : Ministry of Education, Culture, Sports, Science and Technology, Japan
ID : JP16H03179
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science and Technology, Japan
ID : 18K03529
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science and Technology, Japan
ID : JP18K19901
Pays : International
Organisme : Japan Agency for Medical Research and Development
ID : JP18ae0201009
Pays : International
Organisme : Japan Agency for Medical Research and Development
ID : JP17cm0106202
Pays : International

Informations de copyright

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Auteurs

Naoto Yoshinaga (N)

Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Eol Cho (E)

Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Kyoko Koji (K)

Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Yuki Mochida (Y)

Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan.

Mitsuru Naito (M)

Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Kensuke Osada (K)

National Institute of Radiological Science, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 263-8555, Japan.

Kazunori Kataoka (K)

Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan.
Policy Alternatives Research Institute, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
ORCID: 0000-0002-8591-413X

Horacio Cabral (H)

Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
ORCID: 0000-0002-4030-2631

Satoshi Uchida (S)

Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan.
ORCID: 0000-0001-8726-0478

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Classifications MeSH

questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Nanostructures › Bundling mRNA Strands to Prepare...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Conformation d'acide nucléique › Bundling mRNA Strands to Prepare...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Stabilité de l'ARN › Bundling mRNA Strands to Prepare...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Bundling mRNA Strands to Prepare...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Ribonucléases › Bundling mRNA Strands to Prepare...