Abstract
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.
Keywords: Nonviral gene delivery, gene therapy, tumor targeting
Anti-Cancer Agents in Medicinal Chemistry
Title: Nucleic Acid Based Therapeutics for Tumor Therapy
Volume: 6 Issue: 6
Author(s): Manfred Ogris
Affiliation:
Keywords: Nonviral gene delivery, gene therapy, tumor targeting
Abstract: 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.
Export Options
About this article
Cite this article as:
Ogris Manfred, Nucleic Acid Based Therapeutics for Tumor Therapy, Anti-Cancer Agents in Medicinal Chemistry 2006; 6 (6) . https://dx.doi.org/10.2174/187152006778699158
DOI https://dx.doi.org/10.2174/187152006778699158 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Regulation of Apoptosis by Gram-Positive Bacteria: Mechanistic Diversity and Consequences for Immunity
Current Immunology Reviews (Discontinued) Anti-Degenerative Effect of Melatonin on Intervertebral Disc: Protective Contribution against Inflammation, Oxidative Stress, Apoptosis, and Autophagy
Current Drug Targets New Approaches to Target Cancer Stem Cells: Current Scenario
Mini-Reviews in Medicinal Chemistry Radiopharmaceutical: Revolutionary Agents for Diagnosis
Current Radiopharmaceuticals Promotion of Remyelination by Immunoglobulins: Implications for the Treatment of Multiple Sclerosis
Current Pharmaceutical Design Current Status and Future Prospects of C1 Domain Ligands as Drug Candidates
Current Topics in Medicinal Chemistry Neurokinin Receptors and Subtypes as Potential Targets in Breast Cancer: Relevance to Bone Marrow Metastasis
Drug Design Reviews - Online (Discontinued) Recent Advances on the Roles of NO in Cancer and Chronic Inflammatory Disorders
Current Medicinal Chemistry Anticancer and Antimicrobial Evaluations on Alternative Reading Frame (ARF) Peptides and their Derivatives
Protein & Peptide Letters Role of Endogenous Granulocyte-Macrophage Colony Stimulating Factor Following Stroke and Relationship to Neurological Outcome
Current Neurovascular Research Magnesium Lithospermate B Extracted from Salvia Miltiorrhiza, A Potential Substitute for Cardiac Glycosides
Mini-Reviews in Organic Chemistry Pharmacological Modulation of p53 Function in Cancer Therapy
Current Signal Transduction Therapy Small Molecule Kinase Inhibitors as Anti-Cancer Therapeutics
Mini-Reviews in Medicinal Chemistry Mitochondria-Targeting Anticancer Metal Complexes
Current Medicinal Chemistry Mitochondria as Therapeutic Targets of Estrogen Action in the Central Nervous System
Current Drug Targets - CNS & Neurological Disorders Marine Natural Products and Related Compounds as Anticancer Agents: an Overview of their Clinical Status
Anti-Cancer Agents in Medicinal Chemistry Curcumin: A Potential Neuroprotective Agent in Parkinson's Disease
Current Pharmaceutical Design Role of Tumor Microenvironment in Cancer Stem Cells Resistance to Radiotherapy
Current Cancer Drug Targets Systems Medicine Approaches to Improving Understanding, Treatment, and Clinical Management of Neuroendocrine Prostate Cancer
Current Pharmaceutical Design Dietary Phytochemicals in Chemoprevention of Cancer: An Update
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued)