Document Detail


A new generation of human artificial chromosomes for functional genomics and gene therapy.
MedLine Citation:
PMID:  22907415     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Since their description in the late 1990s, human artificial chromosomes (HACs) carrying a functional kinetochore were considered as a promising system for gene delivery and expression with a potential to overcome many problems caused by the use of viral-based gene transfer systems. Indeed, HACs avoid the limited cloning capacity, lack of copy number control and insertional mutagenesis due to integration into host chromosomes that plague viral vectors. Nevertheless, until recently, HACs have not been widely recognized because of uncertainties of their structure and the absence of a unique gene acceptor site. The situation changed a few years ago after engineering of HACs with a single loxP gene adopter site and a defined structure. In this review, we summarize recent progress made in HAC technology and concentrate on details of two of the most advanced HACs, 21HAC generated by truncation of human chromosome 21 and alphoid(tetO)-HAC generated de novo using a synthetic tetO-alphoid DNA array. Multiple potential applications of the HAC vectors are discussed, specifically the unique features of two of the most advanced HAC cloning systems.
Authors:
Natalay Kouprina; William C Earnshaw; Hiroshi Masumoto; Vladimir Larionov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Review     Date:  2012-08-21
Journal Detail:
Title:  Cellular and molecular life sciences : CMLS     Volume:  70     ISSN:  1420-9071     ISO Abbreviation:  Cell. Mol. Life Sci.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-20     Completed Date:  2013-05-13     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  9705402     Medline TA:  Cell Mol Life Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1135-48     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Chromosomes, Artificial, Human / classification,  genetics,  physiology*
Disease Models, Animal
Gene Transfer Techniques
Genetic Diseases, Inborn / genetics,  pathology,  therapy
Genetic Therapy / methods*
Genomics / methods*
Humans
Models, Biological
Grant Support
ID/Acronym/Agency:
073915//Wellcome Trust; 077707//Wellcome Trust; 092076//Wellcome Trust; Z01 BC010413-08/BC/NCI NIH HHS
Comments/Corrections

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