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Updated: Sep 28, 2025

Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
Nucleic acid and oligonucleotide delivery for activating innate immunity in cancer immunotherapy
Fanfei Meng1, Jianping Wang1, Yoon Yeo2
1Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
Abstract:
A group of nucleic acids and oligonucleotides play various roles in the innate immune system. They can stimulate pattern recognition receptors to activate innate immune cells, encode immunostimulatory proteins or peptides, or silence specific genes to block negative regulators of immune cells. Given the limitations of current cancer immunotherapy, there has been increasing interest in harnessing innate immune responses by nucleic acids and oligonucleotides. The poor biopharmaceutical properties of nucleic acids and oligonucleotides make it critical to use carriers that can protect them in circulation, retain them in the tumor microenvironment, and bring them to intracellular targets. Therefore, various gene carriers have been repurposed to deliver nucleic acids and oligonucleotides for cancer immunotherapy and improve their safety and activity. Here, we review recent studies that employed carriers to enhance the functions of nucleic acids and oligonucleotides and overall immune responses to cancer, and discuss remaining challenges and future opportunities in the development of nucleic acid-based immunotherapeutics.
Insights
Nucleic acids and oligonucleotides activate the innate immune system for cancer immunotherapy. Gene carriers improve their delivery and efficacy, enhancing anti-cancer immune responses.
Area of Science:
- Immunology
- Genetics
- Biotechnology
Background:
- Nucleic acids and oligonucleotides are key players in the innate immune system, modulating immune cell activation and gene expression.
- Harnessing innate immunity via nucleic acids and oligonucleotides offers a promising avenue for cancer immunotherapy, addressing limitations of current treatments.
- Poor biopharmaceutical properties of nucleic acids and oligonucleotides necessitate effective delivery systems for therapeutic applications.
Purpose of the Study:
- To review recent advancements in using carriers for nucleic acid and oligonucleotide delivery in cancer immunotherapy.
- To explore how these carriers enhance the function of nucleic acids and oligonucleotides and boost anti-cancer immune responses.
- To discuss current challenges and future directions in developing nucleic acid-based immunotherapeutics.
Main Methods:
- Review of recent scientific literature on gene carriers and nucleic acid/oligonucleotide-based cancer immunotherapy.
- Analysis of studies employing various carriers to improve the delivery, safety, and activity of nucleic acids and oligonucleotides.
- Synthesis of findings related to enhanced immune responses against cancer.
Main Results:
- Gene carriers effectively protect nucleic acids and oligonucleotides in circulation and target them to tumor sites.
- Carriers facilitate intracellular delivery, optimizing the immunostimulatory or gene-silencing functions of nucleic acids and oligonucleotides.
- Repurposed gene carriers have shown potential in improving the safety and efficacy of nucleic acid-based cancer immunotherapies.
Conclusions:
- Carriers are crucial for overcoming the limitations of nucleic acids and oligonucleotides in cancer immunotherapy.
- The strategic use of gene carriers significantly enhances the therapeutic potential of nucleic acid-based immunomodulation.
- Further research into carrier development is essential for advancing nucleic acid-based cancer therapeutics.
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