The Combination of CRISPR/Cas9 and iPSC Technologies in the Gene Therapy of Human β-thalassemia in Mice

Scientific Reports
Zhanhui OuXiaofang Sun

Abstract

β-thalassemia results from point mutations or small deletions in the β-globin (HBB) gene that ultimately cause anemia. The generation of induced pluripotent stem cells (iPSCs) from the somatic cells of patients in combination with subsequent homologous recombination-based gene correction provides new approaches to cure this disease. CRISPR/Cas9 is a genome editing tool that is creating a buzz in the scientific community for treating human diseases, especially genetic disorders. Here, we reported that correction of β-thalassemia mutations in patient-specific iPSCs using the CRISPR/Cas9 tool promotes hematopoietic differentiation in vivo. CRISPR/Cas9-corrected iPSC-derived hematopoietic stem cells (HSCs) were injected into sublethally-irradiated NOD-scid-IL2Rg-/- (NSI) mice. HBB expression was observed in these HSCs after hematopoietic differentiation in the NSI mice. Importantly, no tumor was found in the livers, lungs, kidneys, or bone marrow at 10 weeks in the NSI mice after implantation with these HSCs. Collectively, our findings demonstrated that CRISPR/Cas9 successfully corrects β-thalassemia mutations in patient-specific iPSCs. These CRISPR/Cas9-corrected iPSC-derived HSCs express normal HBB in mice without tumorigenic pot...Continue Reading

References

Sep 16, 2005·The New England Journal of Medicine·Deborah Rund, Eliezer Rachmilewitz
May 4, 2007·Annals of Hematology·George NtaiosStiliani Alexiou-Daniel
Jul 14, 2009·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·Supatra SirichotiyakulTheera Tongsong
Dec 17, 2009·Hemoglobin·Farid BouladMichel Sadelain
May 25, 2010·Orphanet Journal of Rare Diseases·Renzo Galanello, Raffaella Origa
Aug 18, 2010·Annals of the New York Academy of Sciences·D J Weatherall
Aug 18, 2010·Annals of the New York Academy of Sciences·Antonella IsgròGuido Lucarelli
Sep 8, 2010·The Journal of Cell Biology·Daolin TangMichael T Lotze
Mar 16, 2011·The Tohoku Journal of Experimental Medicine·Zhanhui OuXiaofang Sun
May 10, 2011·Nature Reviews. Microbiology·Kira S MakarovaEugene V Koonin
Jun 30, 2012·Science·Martin JinekEmmanuelle Charpentier
Jan 5, 2013·Science·Le CongFeng Zhang
Jan 5, 2013·Science·Prashant MaliGeorge M Church
Feb 5, 2013·Cold Spring Harbor Perspectives in Medicine·Antonio Cao, Yuet Wai Kan
May 28, 2013·Genetics·Scott J GratzKate M O'Connor-Giles
Oct 1, 2013·Nature Methods·Prashant MaliGeorge M Church
Jun 24, 2014·Scientific Reports·Tetsushi SakumaTakashi Yamamoto
May 30, 2015·Journal of Hematology & Oncology·Wei YePeng Li
Mar 26, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xiaofang SunDaolin Tang

Citations

May 26, 2017·Expert Opinion on Investigational Drugs·Irene MottaMaria Domenica Cappellini
Apr 12, 2018·International Journal of Molecular Sciences·Jolene Michelle HelenaAnne Elisabeth Mercier
Feb 8, 2018·European Journal of Immunology·Katharina HochheiserMarco J Herold
Feb 10, 2018·Frontiers in Cardiovascular Medicine·Elisabeth Tamara SträsslerNicolle Kränkel
Jul 18, 2018·Annals of Human Genetics·Sleiman Razzouk
Feb 16, 2018·Human Gene Therapy·Yang YangYuquan Wei
Nov 23, 2018·Nature Reviews. Neuroscience·Mireille KhachoRuth S Slack
Feb 28, 2018·Stem Cell Research & Therapy·Methichit WattanapanitchSurapol Issaragrisil
Apr 5, 2019·Molecular Diagnosis & Therapy·Panayiota PapasavvaCarsten W Lederer
Sep 9, 2020·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Karine Sii-FeliceEmmanuel Payen
Dec 12, 2018·Calcified Tissue International·Lucinda R LeeAaron Schindeler
Mar 25, 2020·Bioscience Reports·Matthew P HirakawaKimberly S Butler
Nov 22, 2017·Journal of Cellular Physiology·Neelam LohaniSivaprakash Ramalingam
May 24, 2017·Science China. Life Sciences·Xiaohui ZhangDali Li
Mar 14, 2019·British Journal of Haematology·Trine I JensenRasmus O Bak
Dec 17, 2020·Expert Opinion on Drug Discovery·Laure Grand MourselAnne-Marie Zuurmond

Related Concepts

Il2rg protein, mouse
Gene Editing
Metazoa
Cell Differentiation Process
Colony-Forming Units, Hematopoietic
Whole-Body Irradiation
Genetic Therapy, Somatic
Gene Expression
Mouse, SCID-hu
Mice, Inbred NOD

Related Feeds

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

CRISPR Genome Editing & Therapy

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of this system for gene editing and therapy in human diseases.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

CRISPR in Cancer

CRISPR-Cas system enables the editing of genes to create or correct mutations. Given that genome instability and mutation is one of the hallmarks of cancer, the CRISPR-Cas system is being explored to genetically alter and eliminate cancer cells. Here is the latest research.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.