Linked Life Data

12032688

Source:http://linkedlifedata.com/resource/pubmed/id/12032688

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2002-5-28
pubmed:abstractText
The ideal gene therapy is one that repairs the precise genetic defect without additional modification of the genome. Such a strategy has been developed for correcting single nucleotide mutations by using RNA/DNA oligonucleotides, or chimeraplasts. This approach for in situ repair is based on the delivery of exogenous DNA designed to mediate genomic base conversion, insertion, or deletion, thereby, correcting the genetic mutation. Using in vivo delivery systems to hepatocytes via the asialoglycoprotein receptor, we targeted rat liver DNA and successfully modified the genomic sequence by chimeraplasty. The changes in both the hepatic genes, and their associated phenotypes remained stable for 2 years. In addition, we also examined the potential to alter sequence defects in mitochondrial DNA. Therefore, we determined whether mitochondria possess the enzymatic machinery for chimeraplast-mediated DNA changes. Using an in vitro DNA repair assay of mutagenized plasmids and an Escherichia coli readout system, we showed that extracts from highly purified rat liver mitochondria have the essential enzymatic activity to mediate precise single-nucleotide changes at a frequency similar to liver nuclear extracts. Moreover, single-stranded oligonucleotides carrying a single nucleotide mismatch with the target sequence were capable of promoting gene conversion using either mitochondrial or nuclear extracts. Several approaches now exist for the precise repair of genetic mutations using either single-stranded or RNA/DNA chimeric oligonucleotides.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
686-90
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Modification of hepatic genomic DNA using RNA/DNA oligonucleotides.
pubmed:affiliation
Department of Medicine, University of Minnesota, Minneapolis, MN 55108, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.