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Nucleic Acids Research, 1991, Vol. 19, No. 4 945-948
© 1991

MOLECULAR BIOLOGY

Antiproliferative effects of antisense oligonucleotides directed to the RNA of c-myc oncogene

Genevieve Degols*, Jean-Paul Leonetti, Nadir Mechti and Bernard Lebleu*

Laboratoire de Biochimie des Proteines, UA CNRS 1191, Université de Montpellier II Sciences et Techniques du Languedoc Place E.Bataillon, 34095 Montpellier cedex, France

* To whom correspondence should be addressed

Received August 1, 1990. Accepted January 24, 1991.

Several groups have reported the use of antisense oligonucleotides to inhibit c-myc gene expression and study its biological role. However high concentrations of free oligonucieotides were generally needed. To lower their concentration and stabilize the antisense effect against c-myc, oligonucleotides were covalently linked to poly(L-lysine) and administered in ternary complexes formed with heparin (100 µg/ml). A sequence specific growth inhibition was observed at concentrations lower than 1µM, while oligonucieotide poly(L-lysine) conjugates alone were inefficient. Similar results occured with other polyanionic compounds. Inhibition of proliferation was correlated to a reduction of c-myc protein and to a transient decrease in c-myc mRNA level. However, implication of RNase H in this process could not be demonstrated.


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