Linked Life Data

7958986

Source:http://linkedlifedata.com/resource/pubmed/id/7958986

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-12-8
pubmed:abstractText
Gene therapy for AIDS requires the identification of genes which effectively inhibit HIV-1 replication coupled to an efficient vector system for gene delivery and expression. Hammerhead ribozymes are RNA molecules capable of catalytic cleavage of complementary RNA molecules. Ribozymes targeted against two portions of the HIV-1 genome were designed to cleave HIV RNA in the tat gene (TAT) or in a common exon for tat and rev (TR). The ribozymes were cloned into the LN (LTR-neomycin) retroviral vector plasmids and expressed as part of viral LTR-driven transcripts. The vectors were packaged as amphitropic virions and used to transduce human T-lymphocytes. Expression of the vector transcripts containing the ribozyme sequences was readily detected by Northern blot analysis of the transduced T cells. The T-lymphocytes expressing the anti-HIV-1 ribozymes showed resistance to HIV-1 replication. In contrast, cells expressing mutant ribozymes, containing substitutions of a key nucleotide in the catalytic domain which cripples the cleavage activity of the ribozymes, supported replication of HIV-1, demonstrating that the functional ribozymes were cleaving the target RNAs. These studies demonstrate that retrovirally transduced ribozymes included in long, multifunctional transcripts, can inhibit HIV replication in human T-lymphocytes. The ribozyme and expression strategies described here should be useful for the gene therapy of AIDS by conferring resistance to HIV-1 replication on cells derived from transduced hematopoietic stem cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0378-1119
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
149
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Inhibition of HIV-1 in human T-lymphocytes by retrovirally transduced anti-tat and rev hammerhead ribozymes.
pubmed:affiliation
Childrens Hospital Los Angeles, Department of Pediatrics, University of Southern California School of Medicine, Los Angeles 90027.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.