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author：

Wu, M. (Wu, M..) [1] | Li, H. (Li, H..) [2] | Zhang, C. (Zhang, C..) [3] | Wang, Y. (Wang, Y..) [4] | Zhang, Y. (Zhang, Y..) [6] | Zhong, A. (Zhong, A..) [7] | Zhang, D. (Zhang, D..) [8] | Liu, X. (Liu, X..) [9]

Indexed by：

Scopus

Abstract：

Immune　checkpoint　blockade　based　on　antibodies　has　shown　great　clinical　success　in　patients,　but　the　transitory　working　manner　leads　to　restricted　therapeutic　benefits.　Herein,　a　genetically　engineered　adenovirus　is　developed　as　the　vector　to　deliver　CRISPR/Cas9　(sgCas9-AdV)　to　achieve　permanent　PD-L1　gene　editing　with　efficiency　up　to　78.7%　exemplified　in　Hepa　1-6　liver　cancer　cells.　Furthermore,　the　sgCas9-AdV　is　loaded　into　hydrogel　made　by　silk　fiber　(SgCas9-AdV/Gel)　for　in　vivo　application.　The　silk-gel　not　only　promotes　local　retention　of　sgCas9-AdV　in　tumor　tissue,　but　also　masks　them　from　host　immune　system,　thus　ensuring　effectively　gene　transduction　over　9　days.　Bearing　these　advantages,　the　sgCas9-AdV/Gel　inhibits　Hepa　1-6　tumor　growth　with　100%　response　rate　by　single-dose　injection,　through　efficient　PD-L1　disruption　to　elicit　a　T　cell-mediated　antitumor　response.　In　addition,　the　sgCas9-AdV/Gel　is　also　successfully　extended　into　other　refractory　tumors.　In　CT26　colon　tumor　characterized　by　poor　response　to　anti-PD-L1,　sgCas9-AdV/Gel　is　demonstrated　to　competent　and　superior　anti-PD-L1　antibody　to　suppress　tumor　progression.　In　highly　aggressive　orthotopic　4T1　mouse　breast　tumor,　such　a　therapeutic　paradigm　significantly　inhibits　primary　tumor　growth　and　induces　a　durable　immune　response　against　tumor　relapse/metastasis.　Thus,　this　study　provides　an　attractive　and　universal　strategy　for　immunotherapy.　©　2023　The　Authors.　Advanced　Science　published　by　Wiley-VCH　GmbH.

Keyword：

adenoviral vector CRISPR/Cas9 immunotherapy PD-L1 gene editing silk-gel

Community：

  • [ 1 ] [Wu, M.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 2 ] [Wu, M.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
  • [ 3 ] [Wu, M.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 4 ] [Wu, M.]Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic Tumors, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 5 ] [Li, H.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 6 ] [Li, H.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 7 ] [Zhang, C.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 8 ] [Zhang, C.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 9 ] [Wang, Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 10 ] [Wang, Y.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
  • [ 11 ] [Wang, Y.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 12 ] [Wang, Y.]Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic Tumors, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 13 ] [Zhang, C.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 14 ] [Zhang, C.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
  • [ 15 ] [Zhang, C.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 16 ] [Zhang, C.]Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic Tumors, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 17 ] [Zhang, Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 18 ] [Zhong, A.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 19 ] [Zhang, D.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 20 ] [Zhang, D.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
  • [ 21 ] [Zhang, D.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 22 ] [Zhang, D.]Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic Tumors, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 23 ] [Liu, X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 24 ] [Liu, X.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
  • [ 25 ] [Liu, X.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 26 ] [Liu, X.]Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic Tumors, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China

Reprint 's Address：

  • [Zhang, D.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, China;;[Liu, X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, China

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Source ：

Advanced Science

ISSN： 2198-3844

Year： 2023

Issue： 12

Volume： 10

1 4 . 3

JCR@2023

1 4 . 3 0 0

JCR@2023

ESI HC Threshold：30

JCR Journal Grade：1

CAS Journal Grade：1

Cited Count：

WoS CC Cited Count：

SCOPUS Cited Count： 1

ESI Highly Cited Papers on the List： 0 Unfold All

WanFang Cited Count：

Chinese Cited Count：

30 Days PV： 0

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