DOI: 10.1073/pnas.91.22.10460. Antisense oligonucleotides adsorbed to polyalkylcyanoacrylate nanoparticles specifically inhibit mutated Ha-ras-mediated cell proliferation and tumorigenicity in nude mice.

Antisense oligonucleotides adsorbed to polyalkylcyanoacrylate nanoparticles specifically inhibit mutated Ha-ras-mediated cell proliferation and tumorigenicity in nude mice.

10.1073/pnas.91.22.10460

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Ras oncogenes owe their transforming properties to single point mutations in the sequence coding for the active site of the p21 protein. These mutations lead to changes in cellular proliferation and induce tumorigenic properties. Point mutations represent a well-defined target for antisense oligonucleotides that can specifically suppress the translation of the targeted mutant mRNA. We show that the stability and cellular disponibility of antisense oligonucleotides can be markedly improved by adsorption to polyalkylcyanoacrylate nanoparticles. Nanoparticle-adsorbed antisense oligonucleotides directed to a point mutation (G-->U) in codon 12 of the Ha-ras mRNA selectively inhibited the proliferation of cells expressing the point-mutated Ha-ras gene at a concentration 100 times lower than free oligonucleotides. In addition they markedly inhibited Ha-ras-dependent tumor growth in nude mice after subcutaneous injection. These experiments show that inhibition of ras oncogenes by antisense oligonucleotides can block tumor development even though ras oncogenic activation might be an early event in tumor progression.

Authors 7

G Schwab (first)
C Chavany (additional)
I Duroux (additional)
G Goubin (additional)
J Lebeau (additional)
C Hélène (additional)
T Saison-Behmoaras (additional)

References 0 Referenced 141

None

Dates

Type	When
Created	19 years, 3 months ago (May 31, 2006, 8:58 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 2:04 p.m.)
Indexed	1 month ago (Aug. 2, 2025, 1:27 a.m.)
Issued	30 years, 10 months ago (Oct. 25, 1994)
Published	30 years, 10 months ago (Oct. 25, 1994)
Published Online	30 years, 10 months ago (Oct. 25, 1994)
Published Print	30 years, 10 months ago (Oct. 25, 1994)

Funders 0

None

BibTeX

@article{Schwab_1994, title={Antisense oligonucleotides adsorbed to polyalkylcyanoacrylate nanoparticles specifically inhibit mutated Ha-ras-mediated cell proliferation and tumorigenicity in nude mice.}, volume={91}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.91.22.10460}, DOI={10.1073/pnas.91.22.10460}, number={22}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Schwab, G and Chavany, C and Duroux, I and Goubin, G and Lebeau, J and Hélène, C and Saison-Behmoaras, T}, year={1994}, month=oct, pages={10460–10464} }

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