Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders

Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders

Vectors used in gene therapy for hemoglobin disorders carry globin in a reverse-orientation to prevent the loss of key regulatory elements by RNA splicing, but this limits their efficiency. Here, the authors develop a vector carrying β-globin in a forward orientation and show that it has improved ti...

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Main Authors: Naoya Uchida, Matthew M. Hsieh, Lydia Raines, Juan J. Haro-Mora, Selami Demirci, Aylin C. Bonifacino, Allen E. Krouse, Mark E. Metzger, Robert E. Donahue, John F. Tisdale
Format: Article
Language:English
Published: Nature Publishing Group 2019-10-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-019-12456-3
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spelling doaj-10b9f0823d304489858931b8d82f9d3e2021-05-11T12:23:27ZengNature Publishing GroupNature Communications2041-17232019-10-0110111410.1038/s41467-019-12456-3Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disordersNaoya Uchida0Matthew M. Hsieh1Lydia Raines2Juan J. Haro-Mora3Selami Demirci4Aylin C. Bonifacino5Allen E. Krouse6Mark E. Metzger7Robert E. Donahue8John F. Tisdale9Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)Translational Stem Cell Biology Branch, NHLBI, NIHTranslational Stem Cell Biology Branch, NHLBI, NIHTranslational Stem Cell Biology Branch, NHLBI, NIHCellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)Vectors used in gene therapy for hemoglobin disorders carry globin in a reverse-orientation to prevent the loss of key regulatory elements by RNA splicing, but this limits their efficiency. Here, the authors develop a vector carrying β-globin in a forward orientation and show that it has improved titers and transduction efficiency in humanized mice and nonhuman primates.https://doi.org/10.1038/s41467-019-12456-3
collection DOAJ
language English
format Article
sources DOAJ
author Naoya Uchida
Matthew M. Hsieh
Lydia Raines
Juan J. Haro-Mora
Selami Demirci
Aylin C. Bonifacino
Allen E. Krouse
Mark E. Metzger
Robert E. Donahue
John F. Tisdale
spellingShingle Naoya Uchida
Matthew M. Hsieh
Lydia Raines
Juan J. Haro-Mora
Selami Demirci
Aylin C. Bonifacino
Allen E. Krouse
Mark E. Metzger
Robert E. Donahue
John F. Tisdale
Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders
Nature Communications
author_facet Naoya Uchida
Matthew M. Hsieh
Lydia Raines
Juan J. Haro-Mora
Selami Demirci
Aylin C. Bonifacino
Allen E. Krouse
Mark E. Metzger
Robert E. Donahue
John F. Tisdale
author_sort Naoya Uchida
title Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders
title_short Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders
title_full Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders
title_fullStr Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders
title_full_unstemmed Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders
title_sort development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders
publisher Nature Publishing Group
series Nature Communications
issn 2041-1723
publishDate 2019-10-01
description Vectors used in gene therapy for hemoglobin disorders carry globin in a reverse-orientation to prevent the loss of key regulatory elements by RNA splicing, but this limits their efficiency. Here, the authors develop a vector carrying β-globin in a forward orientation and show that it has improved titers and transduction efficiency in humanized mice and nonhuman primates.
url https://doi.org/10.1038/s41467-019-12456-3
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