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...
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| Veröffentlicht in: | Nano research 2020-06, Vol.13 (6), p.1576-1585 |
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| creator | Ryu, Jee-Yeon Choi, You Jung Won, Eun-Jeong Hui, Emmanuel Kim, Ho-Shik Cho, Young-Seok Yoon, Tae-Jong |
| description | 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. |
| doi_str_mv | 10.1007/s12274-020-2773-1 |
| format | Article |
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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.</description><identifier>ISSN: 1998-0124</identifier><identifier>EISSN: 1998-0000</identifier><identifier>DOI: 10.1007/s12274-020-2773-1</identifier><language>eng</language><publisher>Beijing: Tsinghua University Press</publisher><subject>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</subject><ispartof>Nano research, 2020-06, Vol.13 (6), p.1576-1585</ispartof><rights>Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c344t-b470cd536c90ced71bb47ed9c6674a48507b688d0bc6c6edec898234b33790793</citedby><cites>FETCH-LOGICAL-c344t-b470cd536c90ced71bb47ed9c6674a48507b688d0bc6c6edec898234b33790793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12274-020-2773-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12274-020-2773-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids></links><search><creatorcontrib>Ryu, Jee-Yeon</creatorcontrib><creatorcontrib>Choi, You Jung</creatorcontrib><creatorcontrib>Won, Eun-Jeong</creatorcontrib><creatorcontrib>Hui, Emmanuel</creatorcontrib><creatorcontrib>Kim, Ho-Shik</creatorcontrib><creatorcontrib>Cho, Young-Seok</creatorcontrib><creatorcontrib>Yoon, Tae-Jong</creatorcontrib><title>Gene editing particle system as a therapeutic approach for drug-resistant colorectal cancer</title><title>Nano research</title><addtitle>Nano Res</addtitle><description>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.</description><subject>Antibodies</subject><subject>Atomic/Molecular Structure and Spectra</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cell death</subject><subject>Chemistry and Materials Science</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Condensed Matter Physics</subject><subject>Drug resistance</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Genetic modification</subject><subject>Genome editing</subject><subject>Growth factors</subject><subject>K-Ras protein</subject><subject>Lipids</subject><subject>Materials Science</subject><subject>Monoclonal antibodies</subject><subject>Mutation</subject><subject>Nanotechnology</subject><subject>Point mutation</subject><subject>Research Article</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Surgical implants</subject><subject>Targeted cancer 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editing particle system as a therapeutic approach for drug-resistant colorectal cancer</title><author>Ryu, Jee-Yeon ; Choi, You Jung ; Won, Eun-Jeong ; Hui, Emmanuel ; Kim, Ho-Shik ; Cho, Young-Seok ; Yoon, Tae-Jong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-b470cd536c90ced71bb47ed9c6674a48507b688d0bc6c6edec898234b33790793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antibodies</topic><topic>Atomic/Molecular Structure and Spectra</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cell death</topic><topic>Chemistry and Materials Science</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Condensed Matter Physics</topic><topic>Drug resistance</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptors</topic><topic>Genetic modification</topic><topic>Genome 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approach for drug-resistant colorectal cancer</atitle><jtitle>Nano research</jtitle><stitle>Nano Res</stitle><date>2020-06-01</date><risdate>2020</risdate><volume>13</volume><issue>6</issue><spage>1576</spage><epage>1585</epage><pages>1576-1585</pages><issn>1998-0124</issn><eissn>1998-0000</eissn><abstract>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.</abstract><cop>Beijing</cop><pub>Tsinghua University Press</pub><doi>10.1007/s12274-020-2773-1</doi><tpages>10</tpages></addata></record> |
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| identifier | ISSN: 1998-0124 |
| ispartof | Nano research, 2020-06, Vol.13 (6), p.1576-1585 |
| issn | 1998-0124 1998-0000 |
| language | eng |
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| source | SpringerLink Journals - AutoHoldings |
| 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 |
| title | Gene editing particle system as a therapeutic approach for drug-resistant colorectal cancer |
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