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Targeted In Situ Gene Correction of Dysfunctional APOE Alleles to Produce Atheroprotective Plasma ApoE3 Protein
Joint Authors
Owen, James S.
Simons, J. Paul
Papaioannou, Ioannis
Source
Cardiology Research and Practice
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-05-07
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Cardiovascular disease is the leading worldwide cause of death.
Apolipoprotein E (ApoE) is a 34-kDa circulating glycoprotein, secreted by the liver and macrophages with pleiotropic antiatherogenic functions and hence a candidate to treat hypercholesterolaemia and atherosclerosis.
Here, we describe atheroprotective properties of ApoE, though also potential proatherogenic actions, and the prevalence of dysfunctional isoforms, outline conventional gene transfer strategies, and then focus on gene correction therapeutics that can repair defective APOE alleles.
In particular, we discuss the possibility and potential benefit of applying in combination two technical advances to repair aberrant APOE genes: (i) an engineered endonuclease to introduce a double-strand break (DSB) in exon 4, which contains the common, but dysfunctional, ε2 and ε4 alleles; (ii) an efficient and selectable template for homologous recombination (HR) repair, namely, an adeno-associated viral (AAV) vector, which harbours wild-type APOE sequence.
This technology is applicable ex vivo, for example to target haematopoietic or induced pluripotent stem cells, and also for in vivo hepatic gene targeting.
It is to be hoped that such emerging technology will eventually translate to patient therapy to reduce CVD risk.
American Psychological Association (APA)
Papaioannou, Ioannis& Simons, J. Paul& Owen, James S.. 2012. Targeted In Situ Gene Correction of Dysfunctional APOE Alleles to Produce Atheroprotective Plasma ApoE3 Protein. Cardiology Research and Practice،Vol. 2012, no. 2012, pp.1-16.
https://search.emarefa.net/detail/BIM-449653
Modern Language Association (MLA)
Papaioannou, Ioannis…[et al.]. Targeted In Situ Gene Correction of Dysfunctional APOE Alleles to Produce Atheroprotective Plasma ApoE3 Protein. Cardiology Research and Practice No. 2012 (2012), pp.1-16.
https://search.emarefa.net/detail/BIM-449653
American Medical Association (AMA)
Papaioannou, Ioannis& Simons, J. Paul& Owen, James S.. Targeted In Situ Gene Correction of Dysfunctional APOE Alleles to Produce Atheroprotective Plasma ApoE3 Protein. Cardiology Research and Practice. 2012. Vol. 2012, no. 2012, pp.1-16.
https://search.emarefa.net/detail/BIM-449653
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-449653