Cationic porphyrins: Novel delivery vehicles for antisense oligodeoxynucleotides

Lyuba Benimetskaya, Garry B. Takle, Maria Vilenchik, Irina Lebedeva, Paul Miller, C. A. Stein

Research output: Contribution to journalArticle

Abstract

Cationic porphyrins form stable complexes with oligodeoxynucleotides. To evaluate delivery, we used a 20mer phosphorothioate oligomer (Isis 3521) targeted to the 3'-untranslated region of the PKC-α mRNA, and complexed it with porphyrin. The expression of PKC-α protein and mRNA in T24 bladder carcinoma cells was reduced by ~ 80 ± 10% at a concentration of oligomer of 3 μM, and 9 μM porphyrin. The expression of PKC-β1, -δ and -ε isoforms was unaffected by this treatment, but elimination of PKC-ζ protein and mRNA were observed. However, treatment with the porphyrin complex of Isis 3522, an oligomer which is directed at the 5' coding region of the PKC-α mRNA, was equally effective as Isis 3521 with respect to PKC-α, but did not affect PKC-ζ protein or mRNA levels. Since Isis 3521 has an 11-base region of complementarity with the PKC-ζ mRNA, wheras Isis 3522 has only a 4-base region, the effect of Isis 3521 on PKC-ζ protein and mRNA expression may be due to irrelevant cleavage. Depending upon the desired application, this new strategy may offer several advantages over other methods of antisense oligodeoxynucleotide delivery including efficiency, stability, solubility, relatively low toxicity and serum compatibility. Porphyrins may thus be a potentially useful delivery vehicle for antisense therapeutics and/or target validation.

Original languageEnglish (US)
Pages (from-to)5310-5317
Number of pages8
JournalNucleic acids research
Volume26
Issue number23
DOIs
StatePublished - Dec 1 1998

ASJC Scopus subject areas

  • Genetics

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    Benimetskaya, L., Takle, G. B., Vilenchik, M., Lebedeva, I., Miller, P., & Stein, C. A. (1998). Cationic porphyrins: Novel delivery vehicles for antisense oligodeoxynucleotides. Nucleic acids research, 26(23), 5310-5317. https://doi.org/10.1093/nar/26.23.5310