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Advancing cancer treatments: The role of oligonucleotide-based therapies in driving progress
Bogdan Dume1, Emilia Licarete2, Manuela Banciu2
1Doctoral School in Integrative Biology, Faculty of Biology and Geology, Babes-Bolyai University, 400006 Cluj-Napoca, Romania.
Abstract:
Although recent advancements in cancer immunology have resulted in the approval of numerous immunotherapies, minimal progress has been observed in addressing hard-to-treat cancers. In this context, therapeutic oligonucleotides, including interfering RNAs, antisense oligonucleotides, aptamers, and DNAzymes, have gained a central role in cancer therapeutic approaches due to their capacity to regulate gene expression and protein function with reduced toxicity compared with conventional chemotherapeutics. Nevertheless, systemic administration of naked oligonucleotides faces many extra- and intracellular challenges that can be overcome by using effective delivery systems. Thus, viral and non-viral carriers can improve oligonucleotide stability and intracellular uptake, enhance tumor accumulation, and increase the probability of endosomal escape while minimizing other adverse effects. Therefore, gaining more insight into fundamental mechanisms of actions of various oligonucleotides and the challenges posed by naked oligonucleotide administration, this article provides a comprehensive review of the recent progress on oligonucleotide delivery systems and an overview of completed and ongoing cancer clinical trials that can shape future oncological treatments.
Insights
Therapeutic oligonucleotides offer a promising approach for hard-to-treat cancers, but effective delivery systems are crucial for their success. This review explores advancements in oligonucleotide delivery, highlighting their potential in future cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Despite advances in cancer immunology, treating difficult cancers remains a challenge.
- Therapeutic oligonucleotides show potential for cancer treatment by regulating gene expression.
- Systemic delivery of naked oligonucleotides faces significant biological barriers.
Purpose of the Study:
- To review recent progress in oligonucleotide delivery systems for cancer therapy.
- To provide an overview of clinical trials involving oligonucleotide-based cancer treatments.
- To highlight the importance of delivery systems in overcoming oligonucleotide administration challenges.
Main Methods:
- Comprehensive literature review of therapeutic oligonucleotides and delivery systems.
- Analysis of mechanisms of action for various oligonucleotide types (interfering RNAs, antisense oligonucleotides, aptamers, DNAzymes).
- Examination of viral and non-viral delivery strategies and their impact on oligonucleotide efficacy.
Main Results:
- Oligonucleotide-based therapies offer reduced toxicity compared to conventional chemotherapy.
- Delivery systems (viral and non-viral carriers) enhance oligonucleotide stability, cellular uptake, and tumor targeting.
- Delivery systems improve endosomal escape, a critical step for intracellular activity.
Conclusions:
- Effective delivery systems are essential to harness the full therapeutic potential of oligonucleotides in oncology.
- Advancements in oligonucleotide delivery systems are critical for developing novel treatments for hard-to-treat cancers.
- Ongoing clinical trials utilizing oligonucleotide delivery systems may shape future cancer treatment paradigms.
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