A chemically unmodified agonistic DNA with growth factor functionality for in vivo therapeutic application.

Aptamers, Nucleotide / chemistry DNA / chemistry Deoxyribonucleases / metabolism Drug Stability Intercellular Signaling Peptides and Proteins / agonists Models, Biological Nucleic Acid Conformation Protein Binding Proto-Oncogene Proteins c-met / chemistry

Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
04 2020
Historique:
received: 05 06 2019
accepted: 19 12 2019
entrez: 10 4 2020
pubmed: 10 4 2020
medline: 16 12 2020
Statut: epublish

Résumé

Although growth factors have great therapeutic potential because of their regenerative functions, they often have intrinsic drawbacks, such as low thermal stability and high production cost. Oligonucleotides have recently emerged as promising chemical entities for designing synthetic alternatives to growth factors. However, their applications in vivo have been recognized as a challenge because of their susceptibility to nucleases and limited distribution to a target tissue. Here, we present the first example of oligonucleotide-based growth factor mimetics that exerts therapeutic effects at a target tissue after systemic injection. The aptamer was designed to dimerize a growth factor receptor for its activation and mitigated the progression of Fas-induced fulminant hepatitis in a mouse model. This unprecedented functionality of the aptamer can be reasonably explained by its high nuclease stability and migration to the liver parenchyma. These mechanistic analyses provided insights for the successful application of aptamer-based receptor agonists.

Identifiants

DOI: 10.1126/sciadv.aay2801 PMID: 32270033 PMC: PMC7112757
pubmed: 32270033
doi: 10.1126/sciadv.aay2801
pii: aay2801
pmc: PMC7112757
doi:

Substances chimiques

Aptamers, Nucleotide 0
Intercellular Signaling Peptides and Proteins 0
DNA 9007-49-2
Proto-Oncogene Proteins c-met EC 2.7.10.1
Deoxyribonucleases EC 3.1.-

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

eaay2801

Informations de copyright

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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Auteurs

Ryosuke Ueki (R)

Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
ORCID: 0000-0002-5433-5354

Satoshi Uchida (S)

Department of Bioengineering, 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

Naoto Kanda (N)

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

Naoki Yamada (N)

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

Ayaka Ueki (A)

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

Momoko Akiyama (M)

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

Kazuko Toh (K)

Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
ORCID: 0000-0003-1448-7131

Horacio Cabral (H)

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

Shinsuke Sando (S)

Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
ORCID: 0000-0003-0275-7237

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Classifications MeSH

questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Polynucléotides › Oligonucléotides › Aptamères nucléotidiques › A chemically unmodified agonistic DNA with...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › A chemically unmodified agonistic DNA with...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Désoxyribonucléases › A chemically unmodified agonistic DNA with...
questionsmedicales.fr › Techniques d'investigation › Stabilité de médicament › A chemically unmodified agonistic DNA with...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › A chemically unmodified agonistic DNA with...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › A chemically unmodified agonistic DNA with...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Conformation d'acide nucléique › A chemically unmodified agonistic DNA with...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › A chemically unmodified agonistic DNA with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes c-met › A chemically unmodified agonistic DNA with...