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...
Main Authors: | , , , , , , , , , |
---|---|
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 |
id |
doaj-10b9f0823d304489858931b8d82f9d3e |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT naoyauchida developmentofaforwardorientedtherapeuticlentiviralvectorforhemoglobindisorders AT matthewmhsieh developmentofaforwardorientedtherapeuticlentiviralvectorforhemoglobindisorders AT lydiaraines developmentofaforwardorientedtherapeuticlentiviralvectorforhemoglobindisorders AT juanjharomora developmentofaforwardorientedtherapeuticlentiviralvectorforhemoglobindisorders AT selamidemirci developmentofaforwardorientedtherapeuticlentiviralvectorforhemoglobindisorders AT aylincbonifacino developmentofaforwardorientedtherapeuticlentiviralvectorforhemoglobindisorders AT allenekrouse developmentofaforwardorientedtherapeuticlentiviralvectorforhemoglobindisorders AT markemetzger developmentofaforwardorientedtherapeuticlentiviralvectorforhemoglobindisorders AT robertedonahue developmentofaforwardorientedtherapeuticlentiviralvectorforhemoglobindisorders AT johnftisdale developmentofaforwardorientedtherapeuticlentiviralvectorforhemoglobindisorders |
_version_ |
1721444890426998784 |