Gene editing particle system as a therapeutic approach for drug-resistant colorectal cancer

The epidermal growth factor receptor (EGFR) pathway plays an important role in the progression of colorectal cancer (CRC). Anti-EGFR drugs based on antibodies have been widely used for treating CRC through inducing the cell death pathway. However, the majority of CRC patients will inevitably develop...

Full description

Saved in:
Bibliographic Details
Published in:Nano research 2020-06, Vol.13 (6), p.1576-1585
Main Authors: Ryu, Jee-Yeon, Choi, You Jung, Won, Eun-Jeong, Hui, Emmanuel, Kim, Ho-Shik, Cho, Young-Seok, Yoon, Tae-Jong
Format: Article
Language:English
Subjects:
Antibodies
Atomic/Molecular Structure and Spectra
Biomedicine
Biotechnology
Cancer
Cell death
Chemistry and Materials Science
Colorectal cancer
Colorectal carcinoma
Condensed Matter Physics
Drug resistance
Epidermal growth factor
Epidermal growth factor receptors
Genetic modification
Genome editing
Growth factors
K-Ras protein
Lipids
Materials Science
Monoclonal antibodies
Mutation
Nanotechnology
Point mutation
Research Article
Ribonucleic acid
RNA
Surgical implants
Targeted cancer therapy
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The epidermal growth factor receptor (EGFR) pathway plays an important role in the progression of colorectal cancer (CRC). Anti-EGFR drugs based on antibodies have been widely used for treating CRC through inducing the cell death pathway. However, the majority of CRC patients will inevitably develop drug-resistance during anti-EGFR drug treatment, which is mainly caused by a point mutation in the KRAS oncogene. We developed a nanoliposomal (NL) particle containing the Cas9 protein and a single-guide RNA (sgRNA) complex (Cas9-RNP), for genomic editing of the KRAS mutation. The NL particle is composed of bio-compatible lipid compounds that can effectively encapsulate Cas9-RNP. By modifying the NL particle to include the appropriate antibody, it can specifically recognize EGFR expressing CRC and effectively deliver the gene-editing complexes. The conditions of NL treatment were optimized using a KRAS mutated CRC in vivo mouse model. Mice with KRAS -mutated CRC showed drug resistance against cetuximab, a therapeutic antibody drug. After treating the mice with the KRAS gene-editing NL particles, the implanted tumors showed a dramatic decrease in size. Our results demonstrated that this genomic editing complex has great potential as a therapeutic carrier system for the treatment of drug-resistant cancer caused by a point mutation.
ISSN:1998-0124
1998-0000
DOI:10.1007/s12274-020-2773-1