Correction of chromosomal point mutations in human cells with bifunctional oligonucleotides View Full Text


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Article Info

DATE

1999-10

AUTHORS

K W Culver, W T Hsieh, Y Huyen, V Chen, J Liu, Y Khripine, A Khorlin

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. More... »

PAGES

nbt1099_989

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/13684

DOI

http://dx.doi.org/10.1038/13684

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1001657769

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10504700


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