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Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?

Lung transplantation is the definitive therapy for patients living with end-stage lung disease. Despite significant progress made in the field, graft survival remains the lowest of all solid organ transplants. Additionally, the lung has among the lowest of organ utilization rates—among eligible dono...

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Autores principales: Gao, Qimeng, DeLaura, Isabel F., Anwar, Imran J., Kesseli, Samuel J., Kahan, Riley, Abraham, Nader, Asokan, Aravind, Barbas, Andrew S., Hartwig, Matthew G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283701/
https://www.ncbi.nlm.nih.gov/pubmed/35844566
http://dx.doi.org/10.3389/fimmu.2022.931524
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author Gao, Qimeng
DeLaura, Isabel F.
Anwar, Imran J.
Kesseli, Samuel J.
Kahan, Riley
Abraham, Nader
Asokan, Aravind
Barbas, Andrew S.
Hartwig, Matthew G.
author_facet Gao, Qimeng
DeLaura, Isabel F.
Anwar, Imran J.
Kesseli, Samuel J.
Kahan, Riley
Abraham, Nader
Asokan, Aravind
Barbas, Andrew S.
Hartwig, Matthew G.
author_sort Gao, Qimeng
collection PubMed
description Lung transplantation is the definitive therapy for patients living with end-stage lung disease. Despite significant progress made in the field, graft survival remains the lowest of all solid organ transplants. Additionally, the lung has among the lowest of organ utilization rates—among eligible donors, only 22% of lungs from multi-organ donors were transplanted in 2019. Novel strategies are needed to rehabilitate marginal organs and improve graft survival. Gene therapy is one promising strategy in optimizing donor allografts. Over-expression or inhibition of specific genes can be achieved to target various pathways of graft injury, including ischemic-reperfusion injuries, humoral or cellular rejection, and chronic lung allograft dysfunction. Experiments in animal models have historically utilized adenovirus-based vectors and the majority of literature in lung transplantation has focused on overexpression of IL-10. Although several strategies were shown to prevent rejection and prolong graft survival in preclinical models, none have led to clinical translation. The past decade has seen a renaissance in the field of gene therapy and two AAV-based in vivo gene therapies are now FDA-approved for clinical use. Concurrently, normothermic ex vivo machine perfusion technology has emerged as an alternative to traditional static cold storage. This preservation method keeps organs physiologically active during storage and thus potentially offers a platform for gene therapy. This review will explore the advantages and disadvantages of various gene therapy modalities, review various candidate genes implicated in various stages of allograft injury and summarize the recent efforts in optimizing donor lungs using gene therapy.
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spelling pubmed-92837012022-07-16 Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality? Gao, Qimeng DeLaura, Isabel F. Anwar, Imran J. Kesseli, Samuel J. Kahan, Riley Abraham, Nader Asokan, Aravind Barbas, Andrew S. Hartwig, Matthew G. Front Immunol Immunology Lung transplantation is the definitive therapy for patients living with end-stage lung disease. Despite significant progress made in the field, graft survival remains the lowest of all solid organ transplants. Additionally, the lung has among the lowest of organ utilization rates—among eligible donors, only 22% of lungs from multi-organ donors were transplanted in 2019. Novel strategies are needed to rehabilitate marginal organs and improve graft survival. Gene therapy is one promising strategy in optimizing donor allografts. Over-expression or inhibition of specific genes can be achieved to target various pathways of graft injury, including ischemic-reperfusion injuries, humoral or cellular rejection, and chronic lung allograft dysfunction. Experiments in animal models have historically utilized adenovirus-based vectors and the majority of literature in lung transplantation has focused on overexpression of IL-10. Although several strategies were shown to prevent rejection and prolong graft survival in preclinical models, none have led to clinical translation. The past decade has seen a renaissance in the field of gene therapy and two AAV-based in vivo gene therapies are now FDA-approved for clinical use. Concurrently, normothermic ex vivo machine perfusion technology has emerged as an alternative to traditional static cold storage. This preservation method keeps organs physiologically active during storage and thus potentially offers a platform for gene therapy. This review will explore the advantages and disadvantages of various gene therapy modalities, review various candidate genes implicated in various stages of allograft injury and summarize the recent efforts in optimizing donor lungs using gene therapy. Frontiers Media S.A. 2022-07-01 /pmc/articles/PMC9283701/ /pubmed/35844566 http://dx.doi.org/10.3389/fimmu.2022.931524 Text en Copyright © 2022 Gao, DeLaura, Anwar, Kesseli, Kahan, Abraham, Asokan, Barbas and Hartwig https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Gao, Qimeng
DeLaura, Isabel F.
Anwar, Imran J.
Kesseli, Samuel J.
Kahan, Riley
Abraham, Nader
Asokan, Aravind
Barbas, Andrew S.
Hartwig, Matthew G.
Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?
title Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?
title_full Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?
title_fullStr Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?
title_full_unstemmed Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?
title_short Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?
title_sort gene therapy: will the promise of optimizing lung allografts become reality?
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283701/
https://www.ncbi.nlm.nih.gov/pubmed/35844566
http://dx.doi.org/10.3389/fimmu.2022.931524
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