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Updated: Jun 4, 2026
In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
Published on: May 5, 2023
Antisense efficacy : site-restricted in vivo and ex vivo models
L M Neckers1, D Geselowitz, C Chavany
1Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD.
Abstract:
In the laboratory, antisense oligodeoxynucleotides (ODN) have repeatedly demonstrated efficacy in modulating the expression of various genes, thus providing important insights into their roles in tumorigenesis or normal growth and development (1-3). Although attention has been focused recently on the development of antisense ODN as therapeutics for a variety of diseases, including cancer (4), systemic application of ODN to treat tumors other than those of the hematopoietic system presents several problems, not least of which is the ability of systemically administered antisense to reach distant tumor sites. This is particularly true when considering tumors of the central nervous system (CNS), such as glioblastomas and HIV-associated B-cell lymphomas. In this case, the blood-brain barrrer poses an additional obstacle to successful delivery of anionic ODN. On the other hand, the intractability of CNS tumors to standard chemotherapy makes them interesting candidates for antisense intervention. The first model system we will discuss mvolves direct mfusron of ODN into the CNS for the purpose of continuous perfusion of tumor cells.
Insights
Antisense oligodeoxynucleotides (ODN) show promise for treating gene expression in cancers. Direct delivery into the central nervous system (CNS) may overcome challenges in reaching brain tumors like glioblastomas.
Area of Science:
- Molecular Biology
- Neuro-Oncology
- Drug Delivery
Background:
- Antisense oligodeoxynucleotides (ODN) effectively modulate gene expression in laboratory settings.
- Systemic delivery of ODN faces challenges, particularly for tumors outside the hematopoietic system, including the central nervous system (CNS).
- The blood-brain barrier presents a significant obstacle for ODN delivery to CNS tumors such as glioblastomas.
Purpose of the Study:
- To explore the potential of antisense ODN as a therapeutic strategy for CNS tumors.
- To address the challenges of delivering antisense ODN to the CNS.
- To investigate direct intrafusion of ODN into the CNS for continuous tumor cell perfusion.
Main Methods:
- Laboratory studies using antisense oligodeoxynucleotides (ODN).
- Investigating gene expression modulation relevant to tumorigenesis and normal development.
- Developing methods for direct intrafusion of ODN into the CNS.
Main Results:
- Antisense ODN demonstrated efficacy in modulating gene expression in preclinical models.
- Direct intrafusion of ODN into the CNS was explored as a delivery method.
- Challenges in systemic ODN delivery to CNS tumors were highlighted.
Conclusions:
- Antisense ODN hold therapeutic potential for CNS tumors, including glioblastomas.
- Direct CNS delivery strategies are crucial for overcoming the blood-brain barrier.
- Further research into ODN delivery is warranted for effective CNS tumor treatment.
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