Nucleic Acid Based Therapeutics for Tumor Therapy

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 16, 12 Issues, 2016

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex

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Nucleic Acid Based Therapeutics for Tumor Therapy

Anti-Cancer Agents in Medicinal Chemistry, 6(6): 563-570.

Author(s): Manfred Ogris.

Affiliation: Pharmaceutical Biology-Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universitat, Butenandtstr. 5-13, D-81377 Munich, Germany.


Although being a heterogeneous disease, cancer has certain characteristic features which can be utilized for treatment with novel macromolecular therapeutics. The active cycling status of tumor cells, proliferating tumor endothelium and a leaky vasculature allow the targeted delivery of therapeutically active nucleic acids into tumor tissue. We and others have developed polycationic gene carriers forming so called polyplexes with nucleic acids. Cellular aspects like binding, internalization and intracellular fate were enlightened. Additionally, virus like domains were incorporated into the polyplex. Hydrophilic shielding domains protect the polyplex from unspecific interaction with blood components, targeting ligands allow cell specific binding and internalization into target cells, and membrane active peptides have a favorable influence on intracellular trafficking. Physical targeting of polyplexes, like locoregional hyperthermia and photochemical internalization (PCI) have been further used to enhance the efficiency of nucleic acid transfer. Therapeutic concepts were carried out in different tumor models in mice. Local application of synthetic, double stranded RNA led to eradication of intracranial glioblastoma. A gene directed enzyme prodrug approach utilizing site directed activation of cyclophosphamide with cytochrome P450 gave first, promising results.


Nonviral gene delivery, gene therapy, tumor targeting.

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Article Details

Volume: 6
Issue Number: 6
First Page: 563
Last Page: 570
Page Count: 8
DOI: 10.2174/187152006778699158
Price: $58

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