Therapeutic In Vivo Gene Editing Achieved by a Hypercompact CRISPR‐Cas12f1 System Delivered with All‐in‐One Adeno‐Associated Virus

CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno‐associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently eng...

Full description

Saved in:
Bibliographic Details
Published inAdvanced science Vol. 11; no. 19; pp. e2308095 - n/a
Main Authors Cui, Tongtong, Cai, Bingyu, Tian, Yao, Liu, Xin, Liang, Chen, Gao, Qingqin, Li, Bojin, Ding, Yali, Li, Rongqi, Zhou, Qi, Li, Wei, Teng, Fei
Format Journal Article
LanguageEnglish
Published Germany John Wiley & Sons, Inc 01.05.2024
John Wiley and Sons Inc
Wiley
Subjects
AAV delivery
Amino acids
Animals
CRISPR
CRISPR-Cas Systems - genetics
CRISPR‐Cas12f1
Dependovirus - genetics
Disease Models, Animal
Efficiency
gene editing
Gene Editing - methods
Gene therapy
Genetic disorders
Genetic Therapy - methods
Genetic Vectors - genetics
Genomes
Humans
Mice
Mutation
Photoreceptors
Proteins
retinitis pigmentosa
Retinitis Pigmentosa - genetics
Retinitis Pigmentosa - therapy
Vectors (Biology)
retinitis pigmentosa
gene therapy
AAV delivery
gene editing
CRISPR‐Cas12f1
Online AccessGet full text

Cover

Abstract CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno‐associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V‐F CRISPR‐Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system‐based gene therapy to treat retinitis pigmentosa in RhoP23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy. A hypercompact mini‐CRISPR system suitable for all‐in‐one AAV delivery, CasMINI_v3.1/ge4.1, is identified to achieve highly efficient and accurate in vivo gene editing. This Cas12f1‐based system is employed to cure retinal degeneration in a mouse model of genetic blindness in this study, suggesting its promising applications for in vivo gene therapy.
AbstractList CRISPR-based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno-associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V-F CRISPR-Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system-based gene therapy to treat retinitis pigmentosa in RhoP23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy.
Abstract CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno‐associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V‐F CRISPR‐Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system‐based gene therapy to treat retinitis pigmentosa in RhoP23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy.
CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno‐associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V‐F CRISPR‐Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system‐based gene therapy to treat retinitis pigmentosa in Rho P23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy. A hypercompact mini‐CRISPR system suitable for all‐in‐one AAV delivery, CasMINI_v3.1/ge4.1, is identified to achieve highly efficient and accurate in vivo gene editing. This Cas12f1‐based system is employed to cure retinal degeneration in a mouse model of genetic blindness in this study, suggesting its promising applications for in vivo gene therapy.
CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno‐associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V‐F CRISPR‐Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system‐based gene therapy to treat retinitis pigmentosa in Rho P23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy.
CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno‐associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V‐F CRISPR‐Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system‐based gene therapy to treat retinitis pigmentosa in RhoP23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy. A hypercompact mini‐CRISPR system suitable for all‐in‐one AAV delivery, CasMINI_v3.1/ge4.1, is identified to achieve highly efficient and accurate in vivo gene editing. This Cas12f1‐based system is employed to cure retinal degeneration in a mouse model of genetic blindness in this study, suggesting its promising applications for in vivo gene therapy.
CRISPR-based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno-associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V-F CRISPR-Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system-based gene therapy to treat retinitis pigmentosa in RhoP23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy.CRISPR-based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno-associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V-F CRISPR-Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system-based gene therapy to treat retinitis pigmentosa in RhoP23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy.
CRISPR-based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno-associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V-F CRISPR-Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system-based gene therapy to treat retinitis pigmentosa in Rho mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy.
Author Cui, Tongtong
Zhou, Qi
Liang, Chen
Li, Rongqi
Li, Wei
Liu, Xin
Teng, Fei
Tian, Yao
Cai, Bingyu
Gao, Qingqin
Li, Bojin
Ding, Yali
AuthorAffiliation 1 Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
3 University of Chinese Academy of Sciences Beijing 101408 China
4 Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101 China
2 Institute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China
AuthorAffiliation_xml – name: 1 Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
– name: 2 Institute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China
– name: 3 University of Chinese Academy of Sciences Beijing 101408 China
– name: 4 Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101 China
Author_xml – sequence: 1
  givenname: Tongtong
  surname: Cui
  fullname: Cui, Tongtong
  organization: Chinese Academy of Sciences
– sequence: 2
  givenname: Bingyu
  surname: Cai
  fullname: Cai, Bingyu
  organization: University of Chinese Academy of Sciences
– sequence: 3
  givenname: Yao
  surname: Tian
  fullname: Tian, Yao
  organization: University of Chinese Academy of Sciences
– sequence: 4
  givenname: Xin
  surname: Liu
  fullname: Liu, Xin
  organization: University of Chinese Academy of Sciences
– sequence: 5
  givenname: Chen
  surname: Liang
  fullname: Liang, Chen
  organization: University of Chinese Academy of Sciences
– sequence: 6
  givenname: Qingqin
  surname: Gao
  fullname: Gao, Qingqin
  organization: University of Chinese Academy of Sciences
– sequence: 7
  givenname: Bojin
  surname: Li
  fullname: Li, Bojin
  organization: University of Chinese Academy of Sciences
– sequence: 8
  givenname: Yali
  surname: Ding
  fullname: Ding, Yali
  organization: University of Chinese Academy of Sciences
– sequence: 9
  givenname: Rongqi
  surname: Li
  fullname: Li, Rongqi
  organization: University of Chinese Academy of Sciences
– sequence: 10
  givenname: Qi
  surname: Zhou
  fullname: Zhou, Qi
  organization: Beijing Institute for Stem Cell and Regenerative Medicine
– sequence: 11
  givenname: Wei
  orcidid: 0000-0001-7864-404X
  surname: Li
  fullname: Li, Wei
  email: liwei@ioz.ac.cn
  organization: Beijing Institute for Stem Cell and Regenerative Medicine
– sequence: 12
  givenname: Fei
  orcidid: 0009-0006-7948-2613
  surname: Teng
  fullname: Teng, Fei
  email: tengfei@ucas.ac.cn
  organization: University of Chinese Academy of Sciences
BackLink https://www.ncbi.nlm.nih.gov/pubmed/38408137$$D View this record in MEDLINE/PubMed
BookMark eNqFkrFu2zAQhoUiRZOmWTsWBLp0sUuKpEROheCkiYEAKeLUK0FRJ5uGLLqkpMBb5059xj5J6To1kixZSOL4_T_vjvc2OWpdC0nynuAxwTj9rKshjFOcUiyw5K-Sk5RIMaKCsaNH5-PkLIQVxphwmjMi3iTHMYwFoflJ8utuCV5voO-sQdMWze3g0CW0gC4q29l2gQqztDBAhcot0uhquwFv3HqjTYcmt9PZt9s_P39PdCBpTdBsGzpYo3No7AA-au5tt0RF00TGtnG5icZFBa2L5yIEZ6zuIja3vg_vkte1bgKcPeynyfevF3eTq9H1zeV0UlyPDM8kG3FRUV5mMhekYkxmOTdc5LEJNGU8yymRmeQp5UKWmNfGVFzQTOQM6ioFnef0NJnufSunV2rj7Vr7rXLaqn8B5xdK-9iOBlRdm7rELNU4lcwQrTEuM55nOs9kTSSPXl_2Xpu-XENloO28bp6YPr1p7VIt3KAIIVhmLIsOnx4cvPvRQ-jU2gYDTaNbcH1QqYx1xWo4jejHZ-jK9b6NvVIUx6yip2CR-vA4pUMu__88AuM9YLwLwUN9QAhWu7lSu7lSh7mKAvZMYGynO-t2JdnmRdm9bWD7wiOqOJ_PYlcZ_QsMf-LW
CitedBy_id crossref_primary_10_3390_jcm13144224
crossref_primary_10_1172_jci_insight_178159
crossref_primary_10_1038_s41467_025_56048_w
crossref_primary_10_3390_biomedicines12081725
crossref_primary_10_3389_fimmu_2024_1490911
crossref_primary_10_3390_cimb46050255
Cites_doi 10.1016/j.cell.2022.03.045
10.1016/j.cell.2023.08.031
10.1016/j.molmed.2020.12.005
10.1371/journal.pone.0018556
10.1093/nar/gkq603
10.1038/s41591-018-0327-9
10.1038/s41467-023-37829-7
10.3390/genes11101120
10.1038/s41575-022-00729-0
10.1126/science.add8643
10.1007/s12033-023-00724-z
10.1038/mt.2008.269
10.1038/cr.2017.57
10.1038/s41929-023-00995-4
10.1016/j.celrep.2022.111418
10.1038/s41589-021-00868-6
10.1093/bioinformatics/btp352
10.1038/nmeth819
10.1093/bioinformatics/btu048
10.1016/j.cell.2020.03.023
10.1126/science.aav4294
10.1146/annurev-genet-071719-030438
10.1016/j.molcel.2021.08.008
10.1038/nrmicro.2016.184
10.1126/science.aan4672
10.1167/iovs.07-0257
10.1038/s41587-019-0032-3
10.1074/jbc.M110.209759
10.1038/s41392-023-01309-7
10.1038/s41589-023-01420-4
10.1038/s41421-018-0069-3
10.1038/s41589-023-01380-9
10.3390/jcm9072224
10.1038/s41573-019-0012-9
10.1038/s41467-022-33346-1
10.1016/j.preteyeres.2017.10.004
10.7554/eLife.30577
10.1093/nar/gkaa208
10.1038/s41586-020-1978-5
10.1126/science.1231143
10.1038/s41587-021-01009-z
10.1093/nar/gkab179
10.1038/s41576-019-0205-4
10.1016/j.cell.2015.09.038
10.1038/s41467-021-26469-4
ContentType Journal Article
Copyright 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH
2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.
2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml – notice: 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH
– notice: 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.
– notice: 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
DBID 24P
AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
3V.
7XB
88I
8FK
8G5
ABUWG
AFKRA
AZQEC
BENPR
CCPQU
DWQXO
GNUQQ
GUQSH
HCIFZ
M2O
M2P
MBDVC
PHGZM
PHGZT
PIMPY
PKEHL
PQEST
PQQKQ
PQUKI
PRINS
Q9U
7X8
5PM
DOA
DOI 10.1002/advs.202308095
DatabaseName Wiley-Blackwell Open Access Titles
CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
ProQuest Central (Corporate)
ProQuest Central (purchase pre-March 2016)
Science Database (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
Research Library (Alumni Edition)
ProQuest Central (Alumni Edition)
ProQuest Central UK/Ireland
ProQuest Central Essentials
ProQuest Central
ProQuest One Community College
ProQuest Central Korea
ProQuest Central Student
Research Library Prep
SciTech Premium Collection
Research Library
Science Database
Research Library (Corporate)
ProQuest Central Premium
ProQuest One Academic (New)
Publicly Available Content Database
ProQuest One Academic Middle East (New)
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
ProQuest Central Basic
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Publicly Available Content Database
Research Library Prep
ProQuest Science Journals (Alumni Edition)
ProQuest Central Student
ProQuest One Academic Middle East (New)
ProQuest Central Basic
ProQuest Central Essentials
ProQuest Science Journals
ProQuest One Academic Eastern Edition
ProQuest Central (Alumni Edition)
SciTech Premium Collection
ProQuest One Community College
Research Library (Alumni Edition)
ProQuest Central China
ProQuest Central
ProQuest One Academic UKI Edition
ProQuest Central Korea
ProQuest Research Library
ProQuest Central (New)
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList Publicly Available Content Database


CrossRef

MEDLINE - Academic
MEDLINE
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: 24P
  name: Wiley Online Library Open Access
  url: https://authorservices.wiley.com/open-science/open-access/browse-journals.html
  sourceTypes: Publisher
– sequence: 3
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 4
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
– sequence: 5
  dbid: BENPR
  name: ProQuest Central
  url: https://www.proquest.com/central
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Sciences (General)
EISSN 2198-3844
EndPage n/a
ExternalDocumentID oai_doaj_org_article_ffcfb042a0294c1aa00b6576a769f195
PMC11109646
38408137
10_1002_advs_202308095
ADVS7694
Genre article
Journal Article
GrantInformation_xml – fundername: China Postdoctoral Science Foundation
  funderid: 2022M713133
– fundername: National Key Research and Development Program
  funderid: 2019YFA0110800; 2019YFA0903800
– fundername: National Natural Science Foundation of China
  funderid: 32201193; 32225030
– fundername: International Partnership Program of Chinese Academy of Sciences
  funderid: 152111KYSB20160004
– fundername: National Key Research and Development Program
  grantid: 2019YFA0110800
– fundername: National Key Research and Development Program
  grantid: 2019YFA0903800
– fundername: National Natural Science Foundation of China
  grantid: 32201193
– fundername: International Partnership Program of Chinese Academy of Sciences
  grantid: 152111KYSB20160004
– fundername: China Postdoctoral Science Foundation
  grantid: 2022M713133
– fundername: National Natural Science Foundation of China
  grantid: 32225030
GroupedDBID 0R~
1OC
24P
53G
5VS
88I
8G5
AAFWJ
AAMMB
AAZKR
ABDBF
ABUWG
ACCMX
ACGFS
ACUHS
ACXQS
ADBBV
ADKYN
ADMLS
ADZMN
AEFGJ
AFBPY
AFKRA
AFPKN
AGXDD
AIDQK
AIDYY
ALMA_UNASSIGNED_HOLDINGS
ALUQN
AOIJS
AVUZU
AZQEC
BCNDV
BENPR
BPHCQ
BRXPI
CCPQU
DWQXO
EBS
GNUQQ
GODZA
GROUPED_DOAJ
GUQSH
HCIFZ
HYE
IAO
IGS
ITC
KQ8
M2O
M2P
O9-
OK1
PHGZM
PHGZT
PIMPY
PQQKQ
PROAC
ROL
RPM
AAHHS
AAYXX
ACCFJ
ADZOD
AEEZP
AEQDE
AIWBW
AJBDE
CITATION
EJD
CGR
CUY
CVF
ECM
EIF
NPM
3V.
7XB
8FK
MBDVC
PKEHL
PQEST
PQUKI
PRINS
Q9U
7X8
5PM
WIN
PUEGO
ID FETCH-LOGICAL-c5694-58d35b69781d449675c58702332456731969523589b05fccd5836874efd2ea773
IEDL.DBID 24P
ISSN 2198-3844
IngestDate Wed Aug 27 01:29:03 EDT 2025
Thu Aug 21 18:35:20 EDT 2025
Fri Jul 11 10:53:24 EDT 2025
Fri Jul 25 06:12:21 EDT 2025
Mon Jul 21 06:06:42 EDT 2025
Tue Jul 01 04:00:04 EDT 2025
Thu Apr 24 23:02:22 EDT 2025
Sun Jul 06 04:45:35 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 19
Keywords retinitis pigmentosa
gene therapy
AAV delivery
gene editing
CRISPR‐Cas12f1
Language English
License Attribution
2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.
This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c5694-58d35b69781d449675c58702332456731969523589b05fccd5836874efd2ea773
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ORCID 0009-0006-7948-2613
0000-0001-7864-404X
OpenAccessLink https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fadvs.202308095
PMID 38408137
PQID 3057611184
PQPubID 4365299
PageCount 10
ParticipantIDs doaj_primary_oai_doaj_org_article_ffcfb042a0294c1aa00b6576a769f195
pubmedcentral_primary_oai_pubmedcentral_nih_gov_11109646
proquest_miscellaneous_2932435853
proquest_journals_3057611184
pubmed_primary_38408137
crossref_primary_10_1002_advs_202308095
crossref_citationtrail_10_1002_advs_202308095
wiley_primary_10_1002_advs_202308095_ADVS7694
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2024-05-01
PublicationDateYYYYMMDD 2024-05-01
PublicationDate_xml – month: 05
  year: 2024
  text: 2024-05-01
  day: 01
PublicationDecade 2020
PublicationPlace Germany
PublicationPlace_xml – name: Germany
– name: Weinheim
– name: Hoboken
PublicationTitle Advanced science
PublicationTitleAlternate Adv Sci (Weinh)
PublicationYear 2024
Publisher John Wiley & Sons, Inc
John Wiley and Sons Inc
Wiley
Publisher_xml – name: John Wiley & Sons, Inc
– name: John Wiley and Sons Inc
– name: Wiley
References 2018; 362
2017; 6
2015; 163
2021; 27
2021; 49
2009; 25
2010; 38
2023; 14
2023; 186
2023; 6
2017; 27
2023; 8
2020; 181
2023; 19
2019; 37
2019; 18
2018; 63
2020; 11
2011; 6
2023; 20
2022; 185
2021; 12
2021; 55
2018; 4
2017; 15
2018; 359
2013; 339
2022; 40
2021; 17
2020; 9
2019; 25
2020; 578
2022; 13
2023; 379
2020; 48
2024; 20
2024; 66
2005; 2
2020; 21
2014; 30
2021; 81
2011; 286
2007; 48
2009; 17
e_1_2_9_30_1
e_1_2_9_31_1
e_1_2_9_11_1
e_1_2_9_34_1
e_1_2_9_10_1
e_1_2_9_35_1
e_1_2_9_13_1
e_1_2_9_32_1
e_1_2_9_12_1
e_1_2_9_33_1
e_1_2_9_15_1
e_1_2_9_38_1
e_1_2_9_14_1
e_1_2_9_39_1
e_1_2_9_17_1
e_1_2_9_36_1
e_1_2_9_16_1
e_1_2_9_37_1
e_1_2_9_19_1
e_1_2_9_18_1
e_1_2_9_41_1
e_1_2_9_42_1
e_1_2_9_20_1
e_1_2_9_40_1
e_1_2_9_22_1
e_1_2_9_45_1
e_1_2_9_21_1
e_1_2_9_46_1
e_1_2_9_24_1
e_1_2_9_43_1
e_1_2_9_23_1
e_1_2_9_44_1
e_1_2_9_8_1
e_1_2_9_7_1
e_1_2_9_6_1
e_1_2_9_5_1
e_1_2_9_4_1
e_1_2_9_3_1
e_1_2_9_2_1
e_1_2_9_1_1
e_1_2_9_9_1
e_1_2_9_26_1
e_1_2_9_25_1
e_1_2_9_28_1
e_1_2_9_27_1
e_1_2_9_29_1
References_xml – volume: 12
  start-page: 6191
  year: 2021
  publication-title: Nat. Commun.
– volume: 379
  year: 2023
  publication-title: Science
– volume: 339
  start-page: 819
  year: 2013
  publication-title: Science
– volume: 81
  start-page: 4333
  year: 2021
  publication-title: Mol. Cell
– volume: 163
  start-page: 759
  year: 2015
  publication-title: Cell
– volume: 578
  start-page: 229
  year: 2020
  publication-title: Nature
– volume: 15
  start-page: 169
  year: 2017
  publication-title: Nat. Rev. Microbiol.
– volume: 6
  year: 2017
  publication-title: Elife
– volume: 38
  year: 2010
  publication-title: Nucleic Acids Res.
– volume: 11
  start-page: 1120
  year: 2020
  publication-title: Genes
– volume: 48
  start-page: 3954
  year: 2007
  publication-title: Invest Ophthalmol. Vis. Sci.
– volume: 25
  start-page: 2078
  year: 2009
  publication-title: Bioinformatics
– volume: 2
  start-page: 905
  year: 2005
  publication-title: Nat. Methods
– volume: 17
  start-page: 463
  year: 2009
  publication-title: Mol. Ther.
– volume: 20
  start-page: 288
  year: 2023
  publication-title: Nat. Rev. Gastroenterol. Hepatol.
– volume: 21
  start-page: 255
  year: 2020
  publication-title: Nat. Rev. Genet.
– volume: 185
  start-page: 2806
  year: 2022
  publication-title: Cell
– volume: 55
  start-page: 453
  year: 2021
  publication-title: Ann. Rev. Genet.
– volume: 49
  start-page: 4120
  year: 2021
  publication-title: Nucleic Acids Res.
– volume: 27
  start-page: 203
  year: 2021
  publication-title: Trends Mol. Med.
– volume: 13
  start-page: 5623
  year: 2022
  publication-title: Nat. Commun.
– volume: 48
  start-page: 5016
  year: 2020
  publication-title: Nucleic Acids Res.
– volume: 63
  start-page: 107
  year: 2018
  publication-title: Prog. Retin. Eye Res.
– volume: 66
  start-page: 179
  year: 2024
  publication-title: Mol. Biotechnol.
– volume: 4
  start-page: 63
  year: 2018
  publication-title: Cell Discov.
– volume: 25
  start-page: 229
  year: 2019
  publication-title: Nat. Med.
– volume: 40
  start-page: 94
  year: 2022
  publication-title: Nat. Biotechnol.
– volume: 14
  start-page: 2046
  year: 2023
  publication-title: Nat. Commun.
– volume: 359
  year: 2018
  publication-title: Science
– volume: 9
  start-page: 2224
  year: 2020
  publication-title: J. Clin. Med.
– volume: 8
  start-page: 36
  year: 2023
  publication-title: Signal Transduct. Target Ther.
– volume: 181
  start-page: 136
  year: 2020
  publication-title: Cell
– volume: 6
  year: 2011
  publication-title: PLoS One
– volume: 27
  start-page: 830
  year: 2017
  publication-title: Cell Res.
– volume: 286
  year: 2011
  publication-title: J. Biol. Chem.
– volume: 6
  start-page: 695
  year: 2023
  publication-title: Nat. Catal.
– volume: 20
  start-page: 180
  year: 2024
  publication-title: Nat. Chem. Biol.
– volume: 37
  start-page: 224
  year: 2019
  publication-title: Nat. Biotechnol.
– volume: 18
  start-page: 358
  year: 2019
  publication-title: Nat. Rev. Drug Discov.
– volume: 19
  start-page: 1384
  year: 2023
  publication-title: Nat. Chem. Biol.
– volume: 30
  start-page: 1473
  year: 2014
  publication-title: Bioinformatics
– volume: 40
  year: 2022
  publication-title: Cell Rep.
– volume: 362
  start-page: 839
  year: 2018
  publication-title: Science
– volume: 186
  start-page: 4920
  year: 2023
  publication-title: Cell
– volume: 17
  start-page: 1132
  year: 2021
  publication-title: Nat. Chem. Biol.
– ident: e_1_2_9_8_1
  doi: 10.1016/j.cell.2022.03.045
– ident: e_1_2_9_40_1
  doi: 10.1016/j.cell.2023.08.031
– ident: e_1_2_9_3_1
  doi: 10.1016/j.molmed.2020.12.005
– ident: e_1_2_9_25_1
  doi: 10.1371/journal.pone.0018556
– ident: e_1_2_9_46_1
  doi: 10.1093/nar/gkq603
– ident: e_1_2_9_37_1
  doi: 10.1038/s41591-018-0327-9
– ident: e_1_2_9_13_1
  doi: 10.1038/s41467-023-37829-7
– ident: e_1_2_9_27_1
  doi: 10.3390/genes11101120
– ident: e_1_2_9_6_1
  doi: 10.1038/s41575-022-00729-0
– ident: e_1_2_9_2_1
  doi: 10.1126/science.add8643
– ident: e_1_2_9_5_1
  doi: 10.1007/s12033-023-00724-z
– ident: e_1_2_9_23_1
  doi: 10.1038/mt.2008.269
– ident: e_1_2_9_29_1
  doi: 10.1038/cr.2017.57
– ident: e_1_2_9_21_1
  doi: 10.1038/s41929-023-00995-4
– ident: e_1_2_9_14_1
  doi: 10.1016/j.celrep.2022.111418
– ident: e_1_2_9_12_1
  doi: 10.1038/s41589-021-00868-6
– ident: e_1_2_9_45_1
  doi: 10.1093/bioinformatics/btp352
– ident: e_1_2_9_24_1
  doi: 10.1038/nmeth819
– ident: e_1_2_9_34_1
  doi: 10.1093/bioinformatics/btu048
– ident: e_1_2_9_1_1
  doi: 10.1016/j.cell.2020.03.023
– ident: e_1_2_9_15_1
  doi: 10.1126/science.aav4294
– ident: e_1_2_9_35_1
  doi: 10.1146/annurev-genet-071719-030438
– ident: e_1_2_9_17_1
  doi: 10.1016/j.molcel.2021.08.008
– ident: e_1_2_9_4_1
  doi: 10.1038/nrmicro.2016.184
– ident: e_1_2_9_7_1
  doi: 10.1126/science.aan4672
– ident: e_1_2_9_32_1
  doi: 10.1167/iovs.07-0257
– ident: e_1_2_9_44_1
  doi: 10.1038/s41587-019-0032-3
– ident: e_1_2_9_31_1
  doi: 10.1074/jbc.M110.209759
– ident: e_1_2_9_10_1
  doi: 10.1038/s41392-023-01309-7
– ident: e_1_2_9_41_1
  doi: 10.1038/s41589-023-01420-4
– ident: e_1_2_9_42_1
  doi: 10.1038/s41421-018-0069-3
– ident: e_1_2_9_39_1
  doi: 10.1038/s41589-023-01380-9
– ident: e_1_2_9_28_1
  doi: 10.3390/jcm9072224
– ident: e_1_2_9_9_1
  doi: 10.1038/s41573-019-0012-9
– ident: e_1_2_9_22_1
  doi: 10.1038/s41467-022-33346-1
– ident: e_1_2_9_26_1
  doi: 10.1016/j.preteyeres.2017.10.004
– ident: e_1_2_9_30_1
  doi: 10.7554/eLife.30577
– ident: e_1_2_9_16_1
  doi: 10.1093/nar/gkaa208
– ident: e_1_2_9_36_1
  doi: 10.1038/s41586-020-1978-5
– ident: e_1_2_9_43_1
  doi: 10.1126/science.1231143
– ident: e_1_2_9_11_1
  doi: 10.1038/s41587-021-01009-z
– ident: e_1_2_9_19_1
  doi: 10.1093/nar/gkab179
– ident: e_1_2_9_38_1
  doi: 10.1038/s41576-019-0205-4
– ident: e_1_2_9_20_1
  doi: 10.1038/s41589-023-01380-9
– ident: e_1_2_9_33_1
  doi: 10.1016/j.cell.2015.09.038
– ident: e_1_2_9_18_1
  doi: 10.1038/s41467-021-26469-4
SSID ssj0001537418
Score 2.341446
Snippet CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a...
CRISPR-based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a...
Abstract CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9...
SourceID doaj
pubmedcentral
proquest
pubmed
crossref
wiley
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage e2308095
SubjectTerms AAV delivery
Amino acids
Animals
CRISPR
CRISPR-Cas Systems - genetics
CRISPR‐Cas12f1
Dependovirus - genetics
Disease Models, Animal
Efficiency
gene editing
Gene Editing - methods
Gene therapy
Genetic disorders
Genetic Therapy - methods
Genetic Vectors - genetics
Genomes
Humans
Mice
Mutation
Photoreceptors
Proteins
retinitis pigmentosa
Retinitis Pigmentosa - genetics
Retinitis Pigmentosa - therapy
Vectors (Biology)
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwELZQT1wQ5RkoyEhIwCFqYjtOclyWVlskHupLvVmOH2qkVRbtS-LGmRO_kV_CjJ0NuwLUC5coiifWxDMTf7bHnwl56Y0pwvSSD1M3XtYpoHyeApRw2rvGMIcT-h8-ysmFeH9VXG0d9YU5YZEeODbcoffGN-BZOmO1MLnWWdZIAMm6lLXP68BeCn3e1mAq7g_mSMuyYWnM2KG2a2TnBsRdZXiYxFYvFMj6_4Yw_0yU3AawoQc6vkvu9NCRjqLK--SW6-6R_T44F_R1zyD95j75fv57VxU96ehlu55RLKZHtsU8Zzoy161bO0ubr1TTCQxG5yEb3Szp-PTk7PPpz28_xnqRM5_TSGpO37kp5nDAOzh3S0fTKci0HVw-QcUj-H_N4H5jbhC7bOerxQNycXx0Pp6k_aELqSlkLdKisrxoJFJhWSFqGE-YAmKacY5LpCVGbF3g_tq6yQqwtC0qLqtSOG-Z02XJH5K9bta5x4SyUjYcatHWWOFF1Qijc-sAk9rSc88Skm6MoEzPSI4HY0xV5FJmCo2mBqMl5NUg_yVycfxT8i3adJBCDu3wADxL9Z6lbvKshBxsPEL1gb1Q8HssJfQPlUjIi6EYQhLXWXTnZitQAzAxoFAAQgl5FB1o0ITDgLrKeZmQase1dlTdLena60D7nSM5rBQSmi144Q1toADXnMGniCf_ozGekttQs4ipngdkbzlfuWcAx5bN8xB5vwCgbDNv
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: ProQuest Central
  dbid: BENPR
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV1Jb9QwFLagvXBBlDVQkJGQgIPVJHa2E5oOU02RKNV0UW-R46WNNErKZGYkrvxy3kucTEds19ixHL8ln5-fv0fIO6tU1IaXbBu6sXHGAOVzBlDCSGsKFRoM6H89iacX4stVdOUCbo1Lq-x9Yuuoda0wRn4Aegk7boDD4tPtd4ZVo_B01ZXQuE92wQWnsPnaPZycnM42UZaIIz1Lz9bohwdSr5GlG5B36mNRiTt_o5a0_09I8_eEybtAtv0THT0iDx2EpKNO5nvknqkekz1npA394JikPz4hP883t6vocUUvy3VNsZlOdIn5znSkbkqzNpoWP6ikU9iULtqsdLWk49nx2emMjWUThDagHbU5_WzmmMkBb2AEl47mc1ZW7BsMOQIPVrNe3NDhslysmqfk4mhyPp4yV3SBqSjOBItSzaMiRiosLUQG-wkVgU2HnOMRaYIWm0V4vzYr_AgkraOUx2kijNWhkUnCn5Gdqq7MC0LDJC44jCK10sKKtBBKBtoAJtWJ5Tb0COsXP1eOkRwLY8zzjks5zFFY-SAsj7wf-t92XBx_7XmIshx6IYd2-6BeXOfOJHNrlS3AZ0k_zIQKpPT9IgYlk0mc2QAH2e81IXeG3eQbNfTI26EZTBLPWWRl6hVMAzAxoFAAQh553inOMBMOG-o04IlH0i2V2prqdktV3rS03wGSw8YihmVrte8_a5ADrjmDTxEv__0dr8gDeEd0SZz7ZGe5WJnXALSWxRtnTb8AJcAlJg
  priority: 102
  providerName: ProQuest
Title Therapeutic In Vivo Gene Editing Achieved by a Hypercompact CRISPR‐Cas12f1 System Delivered with All‐in‐One Adeno‐Associated Virus
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fadvs.202308095
https://www.ncbi.nlm.nih.gov/pubmed/38408137
https://www.proquest.com/docview/3057611184
https://www.proquest.com/docview/2932435853
https://pubmed.ncbi.nlm.nih.gov/PMC11109646
https://doaj.org/article/ffcfb042a0294c1aa00b6576a769f195
Volume 11
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1Lb9QwELagvXBBlOdCWRkJCThE3cSOkxy32622iJbVblv1Fjl-tJFWCdqX1FvPnPiN_BJmnGy2ESDEJYnskeN4ZuzPE_szIe-tUqELL1kXurEi8QDlMw-ghJHWZCowGNA_PROjC_75Kry6t4u_4odoAm7oGa6_RgeX2eJgSxoq9RrptgFCx_Cyh2QX99cie37Ax9soS8iQngVPmIPZtcdizjfMjb3goF1Ea2RyBP5_Qp2_L568D2rdqHT8hDyu4STtV_rfIw9M8ZTs1Q67oB9rVulPz8j38-1OK3pS0Mt8XVLMpkOd49pn2lc3uVkbTbNbKukIJqhzt0JdLelgcjIdT37e_RjIhR9Yn1ZE5_QI2nCNp31SjOfS_mwGMnkBl69QcB_6tBKeNyYAYpf5fLV4Ti6Oh-eDkVcfxOCpUCTcC2PNwkwgPZbmPIE5hgrBzwPG8LdphF6chLjnNsl6IWhfhzETccSN1YGRUcRekJ2iLMwrQoNIZAxKkVppbnmccSV9bQCn6sgyG3SIt1FCqmqWcjwsY5ZW_MpBikpLG6V1yIdG_lvFz_FXyUPUaSOFvNouoZxfp7WbptYqm0E_JntBwpUvZa-XCZiSyUgk1sdC9jcWkdbOvkihy4wEjBkx75B3TTa4Kf57kYUpV1ANwMmATAEcdcjLyoCamoBVAjBjUYfELdNqVbWdU-Q3jgrcR8JYwQU0m7PCf7RBClhnCp_CX_-n_BvyCBJ5tdJzn-ws5yvzFtDYMus6h-uS3f7R6Zcp3A-HZ-NJ18U2fgFc8jOe
linkProvider Wiley-Blackwell
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Jb9NAFB6V9AAXRFkNBQYJBBys2p7xdkAoTVMltA1Vmla9mfEs1FJkl2yoV34Qv5H3vCSN2E69esajWT4_f_PmzfcIeW2k9Ev3kildNyaIbWD5zAYqoYXRqfQ0OvSPBkHvlH869883yM_mLgyGVTY2sTTUqpDoI98BXMKOG-gw_3j5zcasUXi62qTQqGBxoK--w5Zt-qG_B-v7xvP2u6NOz66zCtjSD2Ju-5Fifhqg1pPiPAbCLH0ArccYngGGCMnYxwukcer4MBTlRyyIQq6N8rQIQwbt3iKbnMFWpkU2d7uD4-HKq-MzlINp1CEdb0eoBaqCA9OPHExice3vVyYJ-BOz_T1A8zpxLv98-_fI3Zqy0naFsS2yofP7ZKs2ClP6rlaufv-A_BitbnPRfk7PskVBsZh2VYbx1bQtLzK90IqmV1TQHmyCJ2UUvJzRzrB_cjy0O2LqesallZQ63dNjjByBN9BjTNvjsZ3l9mdosg0Ws7AbeEGFs2wynz4kpzeyHI9IKy9y_YRQLwxSBq0IJRU3PEq5FK7SwIFVaJjxLGI3k5_IWgEdE3GMk0q72UtwsZLlYlnk7bL-ZaX98deau7iWy1qo2V0-KCZfk9oEJMZIk4KNFI4Xc-kK4ThpAKAWYRAbFxvZbpCQ1IZkmqxgb5FXy2IwAXiuI3JdzKEbwMGB9QLxssjjCjjLnjDYwEcuCy0SrUFqravrJXl2UcqMuyhGG_AApq1E33_mIAEedQJD4U__PY6X5HZvdHSYHPYHB8_IHXifVwGk26Q1m8z1cyB5s_RF_WVR8uWmP-Zftr9eAQ
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Jj9MwFLaGjoS4IIa1MICRQMAhauI42wGhThe1DJSqs2huwfHCRKqSoRuaKz-LX8d7Wdqp2E5zjR3LsT-_fH5-_h4hL42UXuFeMoXrxviRBSzftYBKaGF0IplGh_6nkT844R_OvLMd8rO-C4NhlbVNLAy1yiX6yFuAS9hxAx3mLVOFRYy7_fcX3yzMIIUnrXU6jRIih_ryO2zf5u-GXZjrV4z1e8edgVVlGLCk50fc8kLleomPuk-K8wjIs_QAwMx18TwwQHhGHl4mjRLbg89SXuj6YcC1UUyLIHCh3RtkN4Bdkd0guwe90Xiy8fB4LkrD1EqRNmsJtUKFcGD9oY0JLa78CYuEAX9iub8Ha14l0cVfsH-H3K7oK22XeNsjOzq7S_YqAzGnbyoV67f3yI_jzc0uOszoabrKKRbTnkox1pq25XmqV1rR5JIKOoAN8ayIiJcL2pkMj8YTqyPmDjMOLWXVaVdPMYoE3kDvMW1Pp1aaWZ-hyTZYz9yqoQYVTtPZcn6fnFzLdDwgjSzP9CNCWeAnLrQilFTc8DDhUjhKAx9WgXENaxKrHvxYVmromJRjGpc6zizGyYrXk9Ukr9f1L0odkL_WPMC5XNdC_e7iQT77GlfmIDZGmgTspbBZxKUjhG0nPgBcBH5kHGxkv0ZCXBmVebxZAk3yYl0M5gDPeESm8yV0A_g4MGAgYU3ysATOuicubOZDxw2aJNyC1FZXt0uy9LyQHHdQmNbnPgxbgb7_jEEMnOoIPoU__vd3PCc3YRHHH4ejwyfkFrzOy1jSfdJYzJb6KfC9RfKsWliUfLnutfwLYWViNg
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Therapeutic+In+Vivo+Gene+Editing+Achieved+by+a+Hypercompact+CRISPR%E2%80%90Cas12f1+System+Delivered+with+All%E2%80%90in%E2%80%90One+Adeno%E2%80%90Associated+Virus&rft.jtitle=Advanced+science&rft.au=Cui%2C+Tongtong&rft.au=Cai%2C+Bingyu&rft.au=Tian%2C+Yao&rft.au=Liu%2C+Xin&rft.date=2024-05-01&rft.issn=2198-3844&rft.eissn=2198-3844&rft.volume=11&rft.issue=19&rft_id=info:doi/10.1002%2Fadvs.202308095&rft.externalDBID=n%2Fa&rft.externalDocID=10_1002_advs_202308095
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2198-3844&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2198-3844&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2198-3844&client=summon