PMID- 23741009
OWN - NLM
STAT- MEDLINE
DCOM- 20131105
LR  - 20240104
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 122
IP  - 8
DP  - 2013 Aug 22
TI  - Toward eliminating HLA class I expression to generate universal cells from 
      allogeneic donors.
PG  - 1341-9
LID - 10.1182/blood-2013-03-478255 [doi]
AB  - Long-term engraftment of allogeneic cells necessitates eluding immune-mediated 
      rejection, which is currently achieved by matching for human leukocyte antigen 
      (HLA) expression, immunosuppression, and/or delivery of donor-derived cells to 
      sanctuary sites. Genetic engineering provides an alternative approach to avoid 
      clearance of cells that are recognized as "non-self" by the recipient. To this 
      end, we developed designer zinc finger nucleases and employed a "hit-and-run" 
      approach to genetic editing for selective elimination of HLA expression. 
      Electro-transfer of mRNA species coding for these engineered nucleases completely 
      disrupted expression of HLA-A on human T cells, including CD19-specific T cells. 
      The HLA-A(neg) T-cell pools can be enriched and evade lysis by HLA-restricted 
      cytotoxic T-cell clones. Recognition by natural killer cells of cells that had 
      lost HLA expression was circumvented by enforced expression of nonclassical HLA 
      molecules. Furthermore, we demonstrate that zinc finger nucleases can eliminate 
      HLA-A expression from embryonic stem cells, which broadens the applicability of 
      this strategy beyond infusing HLA-disparate immune cells. These findings 
      establish that clinically appealing cell types derived from donors with disparate 
      HLA expression can be genetically edited to evade an immune response and provide 
      a foundation whereby cells from a single donor can be administered to multiple 
      recipients.
FAU - Torikai, Hiroki
AU  - Torikai H
AD  - Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Reik, Andreas
AU  - Reik A
FAU - Soldner, Frank
AU  - Soldner F
FAU - Warren, Edus H
AU  - Warren EH
FAU - Yuen, Carrie
AU  - Yuen C
FAU - Zhou, Yuanyue
AU  - Zhou Y
FAU - Crossland, Denise L
AU  - Crossland DL
FAU - Huls, Helen
AU  - Huls H
FAU - Littman, Nicholas
AU  - Littman N
FAU - Zhang, Ziying
AU  - Zhang Z
FAU - Tykodi, Scott S
AU  - Tykodi SS
FAU - Kebriaei, Partow
AU  - Kebriaei P
FAU - Lee, Dean A
AU  - Lee DA
FAU - Miller, Jeffrey C
AU  - Miller JC
FAU - Rebar, Edward J
AU  - Rebar EJ
FAU - Holmes, Michael C
AU  - Holmes MC
FAU - Jaenisch, Rudolf
AU  - Jaenisch R
FAU - Champlin, Richard E
AU  - Champlin RE
FAU - Gregory, Philip D
AU  - Gregory PD
FAU - Cooper, Laurence J N
AU  - Cooper LJ
LA  - eng
GR  - CA16672/CA/NCI NIH HHS/United States
GR  - CA120956/CA/NCI NIH HHS/United States
GR  - R37 HD045022/HD/NICHD NIH HHS/United States
GR  - R37 CA084198/CA/NCI NIH HHS/United States
GR  - R01 CA120956/CA/NCI NIH HHS/United States
GR  - R01 CA141303/CA/NCI NIH HHS/United States
GR  - CA124782/CA/NCI NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R01 CA124782/CA/NCI NIH HHS/United States
GR  - R01 HD045022/HD/NICHD NIH HHS/United States
GR  - R01 CA084198/CA/NCI NIH HHS/United States
GR  - R01CA087869/CA/NCI NIH HHS/United States
GR  - P01 CA148600/CA/NCI NIH HHS/United States
GR  - R01 CA087869/CA/NCI NIH HHS/United States
GR  - R21 CA116127/CA/NCI NIH HHS/United States
GR  - R33 CA116127/CA/NCI NIH HHS/United States
GR  - CA141303/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130605
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD19)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - EC 3.1.- (Deoxyribonucleases)
SB  - IM
MH  - Antigens, CD19/metabolism
MH  - Base Sequence
MH  - Cell Differentiation
MH  - Cytotoxicity, Immunologic/immunology
MH  - Deoxyribonucleases/*genetics
MH  - Electroporation
MH  - Embryonic Stem Cells/cytology
MH  - Gene Transfer Techniques
MH  - HEK293 Cells
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Humans
MH  - Leukocytes, Mononuclear/cytology
MH  - Molecular Sequence Data
MH  - Protein Engineering
MH  - Stem Cell Transplantation/*methods
MH  - T-Lymphocytes/immunology
MH  - *Transplantation, Homologous
MH  - Zinc Fingers
PMC - PMC3750336
EDAT- 2013/06/07 06:00
MHDA- 2013/11/06 06:00
PMCR- 2014/08/22
CRDT- 2013/06/07 06:00
PHST- 2013/06/07 06:00 [entrez]
PHST- 2013/06/07 06:00 [pubmed]
PHST- 2013/11/06 06:00 [medline]
PHST- 2014/08/22 00:00 [pmc-release]
AID - S0006-4971(20)54231-6 [pii]
AID - 2013/478255 [pii]
AID - 10.1182/blood-2013-03-478255 [doi]
PST - ppublish
SO  - Blood. 2013 Aug 22;122(8):1341-9. doi: 10.1182/blood-2013-03-478255. Epub 2013 
      Jun 5.