Development and antitumor activity of a BCL-2 targeted single-stranded DNA oligonucleotideReportar como inadecuado




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Cancer Chemotherapy and Pharmacology

, Volume 74, Issue 1, pp 151–166

First Online: 16 May 2014Received: 22 November 2013Accepted: 23 April 2014DOI: 10.1007-s00280-014-2476-y

Cite this article as: Rodrigueza, W.V., Woolliscroft, M.J., Ebrahim, AS. et al. Cancer Chemother Pharmacol 2014 74: 151. doi:10.1007-s00280-014-2476-y

Abstract

PNT100 is a 24-base, chemically unmodified DNA oligonucleotide sequence that is complementary to a region upstream of the BCL-2 gene. Exposure of tumor cells to PNT100 results in suppression of proliferation and cell death by a process called DNA interference. PNT2258 is PNT100 that is encapsulated in protective amphoteric liposomes developed to efficiently encapsulate the PNT100 oligonucleotide, provide enhanced serum stability, optimized pharmacokinetic properties and antitumor activity of the nanoparticle both in vivo and in vitro. PNT2258 demonstrates broad antitumor activity against BCL-2-driven WSU-DLCL2 lymphoma, highly resistant A375 melanoma, PC-3 prostate, and Daudi-Burkitt’s lymphoma xenografts. The sequence specificity of PNT100 was demonstrated against three control sequences scrambled, mismatched, and reverse complement all encapsulated in a lipid formulation with identical particle characteristics, and control sequences did not demonstrate antiproliferative activity in vivo or in vitro. PNT2258 is currently undergoing clinical testing to evaluate safety and antitumor activity in patients with recurrent or refractory non-Hodgkin’s lymphoma and additional studies are planned.

KeywordsPNT2258 DNAi BCL-2 Liposomes Anticancer agent Deoxyribonucleic acid interference Electronic supplementary materialThe online version of this article doi:10.1007-s00280-014-2476-y contains supplementary material, which is available to authorized users.

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Autor: Wendi V. Rodrigueza - Michael J. Woolliscroft - Abdul-Shukkur Ebrahim - Robert Forgey - Patrick J. McGovren - Gerold Ende

Fuente: https://link.springer.com/







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