NDLI: Genetic disruption of the KLF1 gene to overexpress the Î³-globin gene using the CRISPR/Cas9 system.

Please wait, while we are loading the content...

Year: 2016 Volume: 18

Year: 2016 Volume: 18 Issue: 10

Adeno-associated virus-mediated colonic secretory expression of HMGB1 A box attenuates experimental colitis in mice.

Promoter optimisation of lentiviral vectors for efficient insulin gene expression in canine mesenchymal stromal cells: potential surrogate beta cells.

A kidney injury molecule-1 (Kim-1) gene reporter in a mouse artificial chromosome: the responsiveness to cisplatin toxicity in immortalized mouse kidney S3 cells.

Association between LEKR1-CCNL1 and IGSF21-KLHDC7A gene polymorphisms and diabetic retinopathy of type 2 diabetes mellitus in the Chinese Han population.

The relationship between polymorphisms of BDNFOS and BDNF genes and heroin addiction in the Han Chinese population.

Genetic disruption of the KLF1 gene to overexpress the Î³-globin gene using the CRISPR/Cas9 system.

A haploid HSV-1 genome platform for vector development: testing of the tetracycline-responsive switch shows interference by infected cell protein 0.

Year: 2016 Volume: 18 Issue: 9

Year: 2016 Volume: 18 Issue: 8

Year: 2016 Volume: 18 Issue: 7

Year: 2016 Volume: 18 Issue: 1-3

Year: 2016 Volume: 18 Issue: 4-6

Year: 2015 Volume: 17

Year: 2014 Volume: 16

Year: 2013 Volume: 15

Year: 2012 Volume: 14

Year: 2011 Volume: 13

Year: 2010 Volume: 12

Year: 2009 Volume: 11

Year: 2008 Volume: 10

Genetic disruption of the KLF1 gene to overexpress the Î³-globin gene using the CRISPR/Cas9 system.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Shariati, Laleh Khanahmad, Hossein Salehi, Mansoor Hejazi, Zahra Rahimmanesh, Ilnaz Tabatabaiefar, Mohammad Amin Modarressi, Mohammad Hossein
Description	Country affiliation: Iran Author Affiliation: Shariati L ( Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.); Khanahmad H ( Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.); Salehi M ( Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.); Hejazi Z ( Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.); Rahimmanesh I ( Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.); Tabatabaiefar MA ( Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.); Modarressi MH ( Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.)
Abstract	BACKGROUND: ß-thalassemia comprises a major group of human genetic disorders involving a decrease in or an end to the normal synthesis of the ß-globin chains of hemoglobin. KLF1 is a key regulatory molecule involved in the Î³- to ß-globin gene switching process directly inducing the expression of the ß-globin gene and indirectly repressing Î³-globin. The present study aimed to investigate the ability of an engineered CRISPR/Cas9 system with respect to disrupting the KLF1 gene to inhibit the Î³- to ß-hemoglobin switching process in K562 cells. METHODS: We targeted three sites on the KLF1 gene, two of which are upstream of codon 288 in exon 2 and the other site being in exon 3. RESULTS: The average indel percentage in the cells transfected with CRISPR a, b and c was approximately 24%. Relative quantification was performed for the assessment of Î³-globin expression. The levels of Î³-globin mRNA on day 5 of differentiation were 8.1-, 7.7- and 1.8-fold in the cells treated with CRISPR/Cas9 a, b and c, respectively,compared to untreated cells. The measurement of HbF expression levels confirmed the same results. CONCLUSIONS: The findings obtained in the present study support the induction of an indel mutation in the KLF1 gene leading to a null allele. As a result, the effect of KLF1 on the expression of BCL11A is decreased and its inhibitory effect on Î³-globin gene expression is removed. Application of CRISPR technology to induce an indel in the KLF1 gene in adult erythroid progenitors may provide a method for activating fetal hemoglobin expression in individuals with ß-thalassemia or sickle cell disease.
File Format	HTM / HTML
ISSN	1099498X
Issue Number	10
Journal	The Journal of Gene Medicine
Volume Number	18
e-ISSN	15212254
Language	English
Publisher	Wiley
Publisher Date	2016-10-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Genetics Drug Discovery Molecular Biology Molecular Medicine Genetics (clinical)

Central Library (ISO-9001:2015 Certified)
Indian Institute of Technology Kharagpur
Kharagpur, West Bengal, India | PIN - 721302

See location in the Map
03222 282435
Mail: support@ndl.gov.in

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in