Ultrasound-activated particles as CRISPR/Cas9 delivery system for androgenic alopecia therapy.

Alopecia / genetics Animals CRISPR-Associated Protein 9 / metabolism CRISPR-Cas Systems Clustered Regularly Interspaced Short Palindromic Repeats Gene Editing
Androgenic alopecia Gene editing Microbubble Nanoliposome Protein delivery

Journal

Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316

Informations de publication

Date de publication:
02 2020
Historique:
received: 23 08 2019
revised: 27 11 2019
accepted: 25 12 2019
pubmed: 7 1 2020
medline: 15 5 2021
entrez: 6 1 2020
Statut: ppublish

Résumé

Compared to a plasmid, viral, and other delivery systems, direct Cas9/sgRNA protein delivery has several advantages such as low off-targeting effects and non-integration, but it still has limitations due to low transfer efficiency. As such, the CRISPR/Cas9 system is being developed in combination with nano-carrier technology to enhance delivery efficiency and biocompatibility. We designed a microbubble-nanoliposomal particle as a Cas9/sgRNA riboprotein complex carrier, which effectively facilitates local delivery to a specific site when agitated by ultrasound activation. In practice, we successfully transferred the protein constructs into dermal papilla cells in the hair follicle of androgenic alopecia animals by microbubble cavitation induced sonoporation of our particle. The delivered Cas9/sgRNA recognized and edited specifically the target gene with high efficiency in vitro and in vivo, thus recovering hair growth. We demonstrated the topical application of ultrasound-activated nanoparticles for androgenic alopecia therapy through the suppression of SRD5A2 protein production by CRISPR-based genomic editing.

Identifiants

DOI: 10.1016/j.biomaterials.2019.119736 PMID: 31901692
pubmed: 31901692
pii: S0142-9612(19)30854-3
doi: 10.1016/j.biomaterials.2019.119736
pii:
doi:

Substances chimiques

CRISPR-Associated Protein 9 EC 3.1.-

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

119736

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Jee-Yeon Ryu (JY)

Lab. of NanoPharmacy, College of Pharmacy, Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou Universtiy, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, South Korea.

Eun-Jeong Won (EJ)

Lab. of NanoPharmacy, College of Pharmacy, Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou Universtiy, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, South Korea.

Han A Reum Lee (HAR)

Lab. of NanoPharmacy, College of Pharmacy, Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou Universtiy, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, South Korea.

Jin Hyun Kim (JH)

Lab. of NanoPharmacy, College of Pharmacy, Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou Universtiy, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, South Korea.

Emmanuel Hui (E)

Lab. of NanoPharmacy, College of Pharmacy, Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou Universtiy, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, South Korea.

Hong Pyo Kim (HP)

Lab. of NanoPharmacy, College of Pharmacy, Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou Universtiy, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, South Korea. Electronic address: ghim@ajou.ac.kr.

Tae-Jong Yoon (TJ)

Lab. of NanoPharmacy, College of Pharmacy, Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou Universtiy, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, South Korea. Electronic address: tjyoon@moogene.com.

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Classifications MeSH

questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Alopécie › Ultrasound-activated particles as CRISPR/Cas9...
questionsmedicales.fr › Eucaryotes › Animaux › Ultrasound-activated particles as CRISPR/Cas9...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées aux CRISPR › Protéine-9 associée à CRISPR › Ultrasound-activated particles as CRISPR/Cas9...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Systèmes CRISPR-Cas › Ultrasound-activated particles as CRISPR/Cas9...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Séquences répétées en tandem › Clustered regularly interspaced short palindromic repeats › Ultrasound-activated particles as CRISPR/Cas9...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Édition de gène › Ultrasound-activated particles as CRISPR/Cas9...