Therapeutically promising PNA complementary to a regulatory sequence for c-myc: Pharmacokinetics in an animal model of human Burkitt's lymphoma

Lidia C. Boffa, Giovanna Cutrona, Michele Cilli, Maria Rita Mariani, Serena Matis, Martina Pastorino, Gianluca Damonte, Enrico Millo, Silvio Roncella, Manlio Ferrarini

Research output: Contribution to journalArticlepeer-review

Abstract

In Burkitt's lymphoma (BL) cells c-myc is often translocated in proximity to the Eμ enhancer of the Ig gene locus. This translocation causes c-myc hyperexpression and an increase in the cells' proliferative capacity. A peptide nucleic acid (PNA) complementary to enhancer Eμ intronic sequence (PNAEμ), linked to a nuclear localization signal (NLS), selectively and specifically blocks the expression of the c-myc oncogene under Eμ control in vitro, suggesting potential therapeutic use. To explore this issue further, we have determined the pharmacokinetics of 14C-labeled PNAEμ in SCID mice where a human tumor is established by inoculation of cells from a BL cell line. The data demonstrate that the compound has a relatively long life in vivo in tissues and, in particular, in BL tumor mass. Furthermore, in this animal model, PNAEμ shows low or no toxicity. All these results are in favor of a successful preclinical application in a BL human tumor animal model of a PNA targeting a regulatory, nontranscribed DNA sequence that can selectively inhibit the hyperexpression of a translocated gene linked to neoplastic cell expansion.

Original languageEnglish
Pages (from-to)85-93
Number of pages9
JournalOligonucleotides
Volume15
Issue number2
DOIs
Publication statusPublished - 2005

ASJC Scopus subject areas

  • Genetics
  • Pharmacology

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