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High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy

The adaptation of adenoviruses as gene delivery tools has resulted in the development of high-capacity adenoviral vectors (HC-AdVs), also known, helper-dependent or “gutless”. Compared with earlier generations (E1/E3-deleted vectors), HC-AdVs retain relevant features such as genetic stability, remar...

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Autores principales: Ricobaraza, Ana, Gonzalez-Aparicio, Manuela, Mora-Jimenez, Lucia, Lumbreras, Sara, Hernandez-Alcoceba, Ruben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279171/
https://www.ncbi.nlm.nih.gov/pubmed/32455640
http://dx.doi.org/10.3390/ijms21103643
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author Ricobaraza, Ana
Gonzalez-Aparicio, Manuela
Mora-Jimenez, Lucia
Lumbreras, Sara
Hernandez-Alcoceba, Ruben
author_facet Ricobaraza, Ana
Gonzalez-Aparicio, Manuela
Mora-Jimenez, Lucia
Lumbreras, Sara
Hernandez-Alcoceba, Ruben
author_sort Ricobaraza, Ana
collection PubMed
description The adaptation of adenoviruses as gene delivery tools has resulted in the development of high-capacity adenoviral vectors (HC-AdVs), also known, helper-dependent or “gutless”. Compared with earlier generations (E1/E3-deleted vectors), HC-AdVs retain relevant features such as genetic stability, remarkable efficacy of in vivo transduction, and production at high titers. More importantly, the lack of viral coding sequences in the genomes of HC-AdVs extends the cloning capacity up to 37 Kb, and allows long-term episomal persistence of transgenes in non-dividing cells. These properties open a wide repertoire of therapeutic opportunities in the fields of gene supplementation and gene correction, which have been explored at the preclinical level over the past two decades. During this time, production methods have been optimized to obtain the yield, purity, and reliability required for clinical implementation. Better understanding of inflammatory responses and the implementation of methods to control them have increased the safety of these vectors. We will review the most significant achievements that are turning an interesting research tool into a sound vector platform, which could contribute to overcome current limitations in the gene therapy field.
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spelling pubmed-72791712020-06-15 High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy Ricobaraza, Ana Gonzalez-Aparicio, Manuela Mora-Jimenez, Lucia Lumbreras, Sara Hernandez-Alcoceba, Ruben Int J Mol Sci Review The adaptation of adenoviruses as gene delivery tools has resulted in the development of high-capacity adenoviral vectors (HC-AdVs), also known, helper-dependent or “gutless”. Compared with earlier generations (E1/E3-deleted vectors), HC-AdVs retain relevant features such as genetic stability, remarkable efficacy of in vivo transduction, and production at high titers. More importantly, the lack of viral coding sequences in the genomes of HC-AdVs extends the cloning capacity up to 37 Kb, and allows long-term episomal persistence of transgenes in non-dividing cells. These properties open a wide repertoire of therapeutic opportunities in the fields of gene supplementation and gene correction, which have been explored at the preclinical level over the past two decades. During this time, production methods have been optimized to obtain the yield, purity, and reliability required for clinical implementation. Better understanding of inflammatory responses and the implementation of methods to control them have increased the safety of these vectors. We will review the most significant achievements that are turning an interesting research tool into a sound vector platform, which could contribute to overcome current limitations in the gene therapy field. MDPI 2020-05-21 /pmc/articles/PMC7279171/ /pubmed/32455640 http://dx.doi.org/10.3390/ijms21103643 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ricobaraza, Ana
Gonzalez-Aparicio, Manuela
Mora-Jimenez, Lucia
Lumbreras, Sara
Hernandez-Alcoceba, Ruben
High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy
title High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy
title_full High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy
title_fullStr High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy
title_full_unstemmed High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy
title_short High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy
title_sort high-capacity adenoviral vectors: expanding the scope of gene therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279171/
https://www.ncbi.nlm.nih.gov/pubmed/32455640
http://dx.doi.org/10.3390/ijms21103643
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