Abstract：
:Peptide nucleic acids (PNAs) can bind to homopurine/homopyrimidine sequences of double-stranded DNA targets in a sequence-specific manner and form [PNA]2/DNA triplexes with single-stranded DNA D-loop structures at the PNA binding sites. These D-loop structures have been found to have a capacity to initiate transcription in vitro. If this strategy can be used to induce transcription of endogenous genes, it may provide a novel approach for gene therapy of many human diseases. Human [beta] globin disorders such as sickle cell anemia and beta-thalassemia are very common genetic diseases that are caused by mutations in the beta-globin gene. When gamma-globin genes are highly expressed in sickle cell patients, the presence of high levels of fetal hemoglobin (HbF, alpha2gamma2) can compensate for the defective beta-globin gene product and such patients have much improved symptoms or are free of disease. However, the gamma-globin genes are developmentally regulated and normally expressed at very low levels (>1%) in adult blood cells. We have investigated the possibility of inducing gamma-globin gene expression with PNAs. Using PNAs designed to bind to the 5' flanking region of the gamma-globin gene, induction of expression of a reporter gene construct was demonstrated both in vitro and in vivo. More importantly, PNA-mediated induction of endogenous gamma-globin gene expression was also demonstrated in K562 human erythroleukemia cells. This result suggests that induction of gamma-globin gene expression with PNAs might provide a new approach for the treatment of sickle cell disease. PNA-induced gene expression strategy also may have implications in gene therapy of other diseases such as genetic diseases, cancer and infectious diseases.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Wang G,Xu X,Pace B,Dean DA,Glazer PM,Chan P,Goodman SR,Shokolenko Idoi
10.1093/nar/27.13.2806keywords:
subject
Has Abstractpub_date
1999-07-01 00:00:00pages
2806-13issue
13eissn
0305-1048issn
1362-4962pii
gkc425journal_volume
27pub_type
杂志文章abstract：:Phage_Finder, a heuristic computer program, was created to identify prophage regions in completed bacterial genomes. Using a test dataset of 42 bacterial genomes whose prophages have been manually identified, Phage_Finder found 91% of the regions, resulting in 7% false positive and 9% false negative prophages. A searc...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkl732
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journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkg571
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pub_type： 杂志文章
doi：10.1093/nar/27.18.3702
更新日期：1999-09-15 00:00:00
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
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更新日期：1982-12-11 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/2.12.2223
更新日期：1975-12-01 00:00:00
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journal_title：Nucleic acids research
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更新日期：2003-05-15 00:00:00
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journal_title：Nucleic acids research
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更新日期：2012-01-01 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
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更新日期：2007-07-01 00:00:00
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更新日期：2021-01-08 00:00:00
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pub_type： 杂志文章
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更新日期：1988-10-11 00:00:00
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journal_title：Nucleic acids research
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pub_type： 杂志文章
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更新日期：2009-09-01 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
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更新日期：2002-10-15 00:00:00
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journal_title：Nucleic acids research
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更新日期：2017-10-13 00:00:00
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
pub_type： 杂志文章
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更新日期：1989-12-11 00:00:00
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更新日期：2016-11-02 00:00:00
