Nucleic acid-based technologies in therapy of malignant gliomas
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Monika Piwecka1, Katarzyna Rolle, Eliza Wyszko
1Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Abstract:
Malignant gliomas are the deadliest brain tumors, which are characterized by highly invasive growth, a rampant genetic instability and intense resistance to apoptosis. Such an aggressive behavior of malignant gliomas is reflected in the resistance to chemo- and radiotherapy and weak prognosis in spite of cytoreduction through surgery. Brain tumors preferentially express a number of specific protein and RNA markers, that may be exploited as potential therapeutic targets in design of the new treatment modalities based on nucleic acids. For almost three decades, a possibility to apply DNA and RNA molecules as anticancer therapeutics have been studied. A variety of antisense oligonucleotides, ribozymes, DNAzymes, and aptamers can be designed to trigger the sequence-specific inhibition of particular mRNA of interest. RNA interference (RNAi) is the latest and the most promising technique in the long line of nucleic acid-based therapeutic technologies. Recently, we designed and implemented the experimental therapy of patients suffering from malignant brain tumors based on application of double-stranded RNA (dsRNA) specific for tenascin-C (TN-C) mRNA. That therapeutic agent, called ATN-RNA, induces RNAi pathway to inhibit the synthesis of TN-C, the extracellular matrix protein which is highly overexpressed in brain tumor tissue. In the chapter specific problems of application of nucleic acid-based technologies in glioma tumors treatment will be discussed.
Insights
Malignant gliomas are aggressive brain tumors resistant to conventional therapies. RNA interference (RNAi) using double-stranded RNA (dsRNA) targeting tenascin-C (TN-C) mRNA offers a novel therapeutic approach for glioma treatment.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Biotechnology
Background:
- Malignant gliomas are aggressive brain tumors with poor prognosis due to invasive growth, genetic instability, and resistance to apoptosis and standard treatments.
- Specific protein and RNA markers in brain tumors present potential therapeutic targets for novel nucleic acid-based treatments.
- Nucleic acid therapeutics, including antisense oligonucleotides, ribozymes, DNAzymes, and aptamers, have been explored for sequence-specific mRNA inhibition.
Purpose of the Study:
- To discuss the application of nucleic acid-based technologies for treating glioma tumors.
- To highlight RNA interference (RNAi) as a promising therapeutic technology.
- To present the development and experimental application of ATN-RNA for malignant brain tumor therapy.
Main Methods:
- Design and application of double-stranded RNA (dsRNA) specific for tenascin-C (TN-C) mRNA.
- Utilizing the RNA interference (RNAi) pathway to inhibit gene expression.
- Experimental therapy in patients with malignant brain tumors.
Main Results:
- Developed ATN-RNA, a therapeutic agent targeting TN-C mRNA.
- Demonstrated the induction of the RNAi pathway by ATN-RNA.
- TN-C, an extracellular matrix protein overexpressed in brain tumors, was inhibited.
Conclusions:
- Nucleic acid-based therapies, particularly RNAi, hold promise for treating malignant gliomas.
- Targeting overexpressed proteins like TN-C via RNAi is a viable strategy.
- Further discussion on the challenges and potential of these technologies in glioma treatment is warranted.
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