Cited by 73CRISPR and Genetic EngineeringRNA Interference and Gene DeliveryDendrimers and Hyperbranched Polymers

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

A Duplex CRISPR-Cas9 Ribonucleoprotein Nanomedicine for Colorectal Cancer Gene Therapy

Abstract

Based on the high frequency of concurrent adenomatous polyposis coli ( APC ) and KRAS mutations and their strong cooperative interaction in human colorectal cancer (CRC) promotion, we herein develop a CRISPR-Cas9-based genome-editing nanomedicine to target both APC and KRAS mutations for the treatment of CRC. To this end, a hyaluronic acid (HA)-decorated phenylboronic dendrimer (HAPD) was designed for the targeted delivery of Cas9 ribonucleoprotein (RNP), by which both APC and KRAS genetic mutations harboring in CRC cells can be synergistically disrupted. Systemic administration of Cas9 RNP targeting APC and KRAS enabled by HAPD significantly inhibits tumor growth on xenografted and orthotopic CRC mouse models and also greatly prevents CRC-induced liver metastasis and lung metastasis. Thus, this duplex genome-editing system provides a promising gene therapy strategy for the treatment of human CRC and can be extended to other types of cancers with activated Wnt/β-catenin and RAS/extracellular signal-regulated kinase (ERK) pathways.

Overview

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Crossref · 10.1021/acs.nanolett.1c03708

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Metadata

Authors
Wan, T., Pan, Q., Liu, C., Guo, J., Li, B., Yan, X., Cheng, Y., & Ping, Y.
Affiliations
  • Zhejiang University (CN)
  • East China Normal University (CN)
  • College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Corresponding author
Cheng, Yiyun
Venue
Nano Letters
Published
2021-11-12
Volume
21
Issue
22
Pages
9761-9771
ISSN
  • 1530-6984 (ISSN-L)
  • 1530-6992
OpenAlex
W3212753789
Cited by
73
References
40
Citations by year
2026: 9 · 2025: 9 · 2024: 22 · 2023: 22 · 2022: 11
FWCI
3.85
Type
journal article
Language
en
Open access
closed
Locations
  • Nano Letters (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (82073779)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
colorectal cancer, CRISPR/Cas9, APC mutation, KRAS mutation, hyaluronic acid, targeted delivery, genome editing, liver metastasis, lung metastasis, Wnt/β-catenin signaling, Ras/ERK pathway, gene therapy
MeSH terms
Animals, Ribonucleoproteins, Colorectal Neoplasms, Genetic Therapy, Nanomedicine, Mice, Wnt Signaling Pathway, CRISPR-Cas Systems

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