Abstract:
:A sequence-specific genomic delivery system for the correction of chromosomal mutations was designed by incorporating two different binding domains into a single-stranded oligonucleotide. A repair domain (RD) contained the native sequence of the target region. A third strand-forming domain (TFD) was designed to form a triplex by Hoogsteen interactions. The design was based upon the premise that the RD will rapidly form a heteroduplex that is anchored synergistically by the TFD. Deoxyoligonucleotides were designed to form triplexes in the human adenosine deaminase (ADA) and p53 genes adjacent to known point mutations. Transfection of ADA-deficient human lymphocytes corrected the mutant sequence in 1-2% of cells. Neither the RD or TFD individually corrected the mutation. Transfection of p53 mutant human glioblastoma cells corrected the mutation and induced apoptosis in 7.5% of cells.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Culver KW,Hsieh WT,Huyen Y,Chen V,Liu J,Khripine Y,Khorlin Adoi
10.1038/13684subject
Has Abstractpub_date
1999-10-01 00:00:00pages
989-93issue
10eissn
1087-0156issn
1546-1696journal_volume
17pub_type
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