Lentiviral Engineered Fibroblasts Expressing Codon-Optimized COL7A1 Restore Anchoring Fibrils in RDEB

The Journal of Investigative Dermatology
Christos GeorgiadisWaseem Qasim

Abstract

Cells therapies, engineered to secrete replacement proteins, are being developed to ameliorate otherwise debilitating diseases. Recessive dystrophic epidermolysis bullosa (RDEB) is caused by defects of type VII collagen, a protein essential for anchoring fibril formation at the dermal-epidermal junction. Whereas allogeneic fibroblasts injected directly into the dermis can mediate transient disease modulation, autologous gene-modified fibroblasts should evade immunological rejection and support sustained delivery of type VII collagen at the dermal-epidermal junction. We demonstrate the feasibility of such an approach using a therapeutic grade, self-inactivating-lentiviral vector, encoding codon-optimized COL7A1, to transduce RDEB fibroblasts under conditions suitable for clinical application. Expression and secretion of type VII collagen was confirmed with transduced cells exhibiting supranormal levels of protein expression, and ex vivo migration of fibroblasts was restored in functional assays. Gene-modified RDEB fibroblasts also deposited type VII collagen at the dermal-epidermal junction of human RDEB skin xenografts placed on NOD-scid IL2Rgamma(null) recipients, with reconstruction of human epidermal structure and regenerati...Continue Reading

Citations

Mar 30, 2018·Pediatric Research·Michael Vanden OeverJakub Tolar
Oct 28, 2019·Cold Spring Harbor Perspectives in Biology·Laura De RosaMichele De Luca
Mar 4, 2017·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Wei QianDai-Zhi Peng
Jan 27, 2017·Science Translational Medicine·Waseem QasimPaul Veys
Mar 23, 2018·International Journal of Molecular Sciences·Mark J OsbornJakub Tolar
Apr 25, 2019·Expert Opinion on Therapeutic Patents·Mariel Dourado AlcorteMarcos Angelo Demasi
Feb 23, 2020·Tissue Engineering. Part C, Methods·Alex E LaroseLucie Germain
Jan 1, 2016·Npj Regenerative Medicine·Beau R WebberJakub Tolar
Oct 4, 2017·Nucleic Acids Research·Patricia PekingEva M Murauer
May 30, 2019·Experimental Dermatology·Christine ProdingerMartin Laimer
May 31, 2019·Emerging Topics in Life Sciences·Gaetano Naso, Anastasia Petrova
Oct 24, 2020·Expert Opinion on Emerging Drugs·Matthias TiteuxAlain Hovnanian
May 30, 2021·Bulletin of Experimental Biology and Medicine·I I RyuminaG T Zubkov
May 18, 2021·Frontiers in Genetics·Ulrich Koller, Johann W Bauer
Jul 23, 2021·Advanced Drug Delivery Reviews·Ming ZengWenxin Wang

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Methods Mentioned

BETA
xenograft
transmission electron microscopy
flow cytometry
xenografts
biopsies
Electrophoresis

Software Mentioned

ImageJ
Pro
Image

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