Hexon modification of human adenovirus type 5 vectors enables efficient transduction of human multipotent mesenchymal stromal cells.
ATMPs
HAdV-5
adenovirus
capsid modification
gene delivery
gene therapy
mesenchymal stem cells
mesenchymal stromal cells
novel vector development
viral vectors
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
09 Jun 2022
09 Jun 2022
Historique:
received:
10
01
2022
accepted:
04
03
2022
entrez:
11
4
2022
pubmed:
12
4
2022
medline:
12
4
2022
Statut:
epublish
Résumé
In adenovirus type 5 (HAdV-5)-derived viral vectors, the fiber protein has been the preferred locale for modifications to alter the natural viral tropism. Hexon, the most abundant capsid protein, has rarely been used for retargeting purposes, likely because the insertion of larger targeting peptides into Hexon often interferes with the assembly of the viral capsid. We previously observed that positively charged molecules enhance the transduction of human multipotent mesenchymal stromal cells (hMSCs)-a cell type of significant interest for clinical development but inefficiently transduced by unmodified HAdV-5-based vectors. As efficient HAdV-5-mediated gene transfer would greatly increase the therapeutic potential of hMSCs, we tested the hypothesis that introducing positively charged amino acids into Hexon might enhance the transduction of hMSCs, enabling efficient expression of selected transgenes. From the constructs that could be rescued as functional virions, one (HAdV-5-HexPos3) showed striking transduction of hMSCs with up to 500-fold increased efficiency. Evaluation of the underlying mechanism identified heparan sulfate proteoglycans (HSPGs) to be essential for virus uptake by the cells. The ease and efficiency of transduction of hMSCs with this vector will facilitate the development of genetically modified hMSCs as therapeutic vehicles in different disciplines, including oncology or regenerative medicine.
Identifiants
pubmed: 35402633
doi: 10.1016/j.omtm.2022.03.004
pii: S2329-0501(22)00034-1
pmc: PMC8956844
doi:
Types de publication
Journal Article
Langues
eng
Pagination
96-110Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests. A patent application has been filed relating to this work by Ulm University (European patent application #19 204,420.4).
Références
Stem Cell Rev Rep. 2017 Dec;13(6):741-756
pubmed: 28812219
Blood. 2009 Feb 26;113(9):1909-18
pubmed: 19131551
Front Cell Dev Biol. 2022 Jan 14;9:716853
pubmed: 35096805
Blood. 2006 Oct 15;108(8):2554-61
pubmed: 16788098
Stem Cells. 2008 Mar;26(3):831-41
pubmed: 18192232
J Virol. 2003 Oct;77(20):11072-81
pubmed: 14512555
Blood. 2003 Feb 15;101(4):1284-9
pubmed: 12393514
Int J Mol Sci. 2017 Mar 23;18(4):
pubmed: 28420073
Hum Gene Ther. 2014 Apr;25(4):339-49
pubmed: 24512117
Gene Ther. 2008 May;15(10):730-8
pubmed: 18401438
Blood. 2010 Oct 14;116(15):2656-64
pubmed: 20610817
Breast Cancer Res Treat. 2007 Oct;105(2):157-67
pubmed: 17221158
Cytotherapy. 2019 Apr;21(4):468-482
pubmed: 30926359
J Tissue Eng Regen Med. 2020 Nov;14(11):1581-1591
pubmed: 32761798
J Virol. 1996 Nov;70(11):7498-509
pubmed: 8892868
Gene Ther. 2005 Oct;12 Suppl 1:S18-27
pubmed: 16231052
Gene Ther. 2000 Oct;7(20):1707-14
pubmed: 11083491
Curr Gene Ther. 2013 Dec;13(6):421-33
pubmed: 24279313
Artif Cells Nanomed Biotechnol. 2017 May;45(3):544-550
pubmed: 27002739
Mol Ther. 2006 Jul;14(1):118-28
pubmed: 16580883
Biomaterials. 2006 Oct;27(28):4993-5002
pubmed: 16765437
Annu Rev Biochem. 1999;68:729-77
pubmed: 10872465
J Tissue Eng Regen Med. 2017 May;11(5):1354-1364
pubmed: 26053555
Gynecol Oncol. 2002 May;85(2):260-5
pubmed: 11972385
J Biol Chem. 2013 May 10;288(19):13204-14
pubmed: 23543734
J Control Release. 2016 Aug 10;235:379-392
pubmed: 27302248
J Orthop Res. 2008 Mar;26(3):314-21
pubmed: 17960657
J Virol. 1998 Oct;72(10):7909-15
pubmed: 9733828
Stem Cells Int. 2017;2017:3615729
pubmed: 28781596
Cytotherapy. 2012 May;14(5):540-54
pubmed: 22296115
J Virol. 2000 Nov;74(22):10508-13
pubmed: 11044095
Stem Cell Res Ther. 2011 Mar 07;2(2):12
pubmed: 21385372
Signal Transduct Target Ther. 2021 Feb 8;6(1):53
pubmed: 33558455
Gene Ther. 2012 Jan;19(1):109-13
pubmed: 21677690
Cancer Gene Ther. 2010 Jul;17(7):476-83
pubmed: 20168350
J Gene Med. 2004 Feb;6 Suppl 1:S164-71
pubmed: 14978759
Virology. 2009 Mar 15;385(2):434-43
pubmed: 19144372
Vaccine. 2010 Jan 22;28(4):950-7
pubmed: 19925902
J Virol. 2004 Jan;78(1):9-22
pubmed: 14671083
Science. 1997 Feb 28;275(5304):1320-3
pubmed: 9036860
Oncotarget. 2017 Jul 11;8(28):45415-45431
pubmed: 28525366
iScience. 2019 May 31;15:421-438
pubmed: 31121468
Curr Protoc Mouse Biol. 2018 Dec;8(4):e58
pubmed: 30485696
Cytotherapy. 2013 Jun;15(6):641-8
pubmed: 23570660
PLoS One. 2012;7(8):e43255
pubmed: 22905242
J Invest Dermatol. 2014 Feb;134(2):526-537
pubmed: 23921952
Hum Gene Ther. 2001 Oct 10;12(15):1893-905
pubmed: 11589831
J Virol. 2005 Oct;79(20):12635-42
pubmed: 16188965
Sci Transl Med. 2020 Nov 25;12(571):
pubmed: 33239388
Cell Physiol Biochem. 2017;43(4):1648-1662
pubmed: 29045937
Viruses. 2021 Jun 12;13(6):
pubmed: 34204818
Cytotherapy. 2006;8(4):315-7
pubmed: 16923606
Biomedicines. 2018 Jul 26;6(3):
pubmed: 30049954
J Biol Chem. 2011 Jul 15;286(28):24535-43
pubmed: 21596747
Mol Ther. 2020 Apr 8;28(4):1033-1042
pubmed: 32053771
Gene Ther. 2008 May;15(10):711-5
pubmed: 18356815
Virology. 2012 Feb 5;423(1):6-13
pubmed: 22169623
PLoS Pathog. 2010 Oct 07;6(10):e1001142
pubmed: 20949078
JAMA Oncol. 2017 Jun 01;3(6):841-849
pubmed: 27441411
Gene Ther. 2007 Jan;14(1):58-67
pubmed: 16900223
Hum Gene Ther. 2000 Oct 10;11(15):2105-16
pubmed: 11044912
J Immunol. 2005 Jun 1;174(11):7179-85
pubmed: 15905562
Nat Med. 2013 Apr;19(4):452-7
pubmed: 23524342
Leukemia. 2018 Jul;32(7):1529-1541
pubmed: 29654266
J Gene Med. 2007 Jul;9(7):579-84
pubmed: 17533614
Orthop Traumatol Surg Res. 2014 Feb;100(1 Suppl):S107-12
pubmed: 24411717
Biomaterials. 2014 Jul;35(21):5627-35
pubmed: 24731711
J Virol. 2000 Mar;74(6):2804-13
pubmed: 10684297
J Gen Virol. 2000 Nov;81(Pt 11):2605-2609
pubmed: 11038370
Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):4344–4354
pubmed: 28810264
Hum Gene Ther. 1996 Nov 10;7(17):2101-12
pubmed: 8934224
Diabetes Res Clin Pract. 2011 Aug;93(2):228-234
pubmed: 21632142
Virology. 2005 Mar 15;333(2):284-92
pubmed: 15721362
Blood. 2009 Jul 30;114(5):965-71
pubmed: 19429866
Int J Cancer. 2015 Aug 15;137(4):978-90
pubmed: 25604186
Adv Drug Deliv Rev. 2012 Jun 1;64(8):720-9
pubmed: 22212901
Oncolytic Virother. 2015 Oct 14;4:149-55
pubmed: 27512678
Cell Biochem Biophys. 2013;67(3):1181-91
pubmed: 23712865
Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5483-8
pubmed: 18391209
Mol Cancer Ther. 2006 Mar;5(3):755-66
pubmed: 16546991
Annu Rev Biochem. 2014;83:129-57
pubmed: 24606135