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Updated: Mar 31, 2026
Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
Assembled DNA Nanostructure to Precisely Induced cGAS-STING Activation for Cancer Immunotherapy
Li He1, Yu Zhang2, Shujuan Cao1
1School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, China.
Abstract:
Triple-negative breast cancer (TNBC) has emerged as a major challenge in cancer therapy due to its aggressive nature and lack of effective targeted treatments. Activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway to stimulate innate immunity is considered a promising strategy for TNBC treatment. However, current STING agonists are limited by several severe drawbacks that hinder their further application. Herein, a cross-shaped DNA skeleton was rationally engineered by leveraging programmable DNA assembly and AS1411 aptamer-mediated tumor targeting to achieve specific activation of the cGAS-STING pathway. The DNA nanoarchitecture exhibited outstanding resistance to nuclease-mediated degradation and achieved nucleolin-targeted cellular internalization, thereby facilitating efficient activation of the cGAS-STING signaling cascade and eliciting potent innate immune responses. In vitro and in vivo evaluations further validated that the DNA scaffold not only triggered innate immune activation but also inhibited tumor progression in TNBC models. Overall, this work provides a promising strategy for the development of safe and effective TNBC immunotherapy.
Insights
Researchers developed a novel DNA nanoarchitecture to target triple-negative breast cancer (TNBC). This approach activates the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, stimulating innate immunity for effective TNBC immunotherapy.
Area of Science:
- Biotechnology
- Immunology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to its aggressive nature and limited targeted treatment options.
- Activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway offers a promising strategy to enhance innate immunity against TNBC.
- Existing STING agonists face limitations that impede their clinical application.
Purpose of the Study:
- To engineer a novel DNA nanoarchitecture for targeted activation of the cGAS-STING pathway in TNBC.
- To overcome the limitations of current STING agonists through programmable DNA assembly and aptamer-mediated targeting.
- To evaluate the efficacy of the DNA nanoarchitecture in triggering innate immune responses and inhibiting TNBC progression.
Main Methods:
- Rational engineering of a cross-shaped DNA skeleton using programmable DNA assembly.
- Incorporation of the AS1411 aptamer for nucleolin-targeted delivery and cellular internalization.
- Assessment of nuclease resistance and cellular uptake of the DNA nanoarchitecture.
- Evaluation of cGAS-STING pathway activation and innate immune response stimulation in vitro and in vivo.
- Testing the therapeutic efficacy of the DNA scaffold in TNBC models.
Main Results:
- The engineered DNA nanoarchitecture demonstrated enhanced resistance to nuclease degradation.
- Nucleolin-targeted cellular internalization was achieved via the AS1411 aptamer.
- Efficient activation of the cGAS-STING signaling cascade and potent innate immune responses were observed.
- The DNA scaffold effectively inhibited tumor progression in TNBC models.
- In vitro and in vivo studies confirmed the potential of the DNA structure in immunotherapy.
Conclusions:
- The developed DNA nanoarchitecture represents a promising strategy for TNBC immunotherapy.
- Targeted activation of the cGAS-STING pathway using this novel scaffold can elicit robust innate immune responses.
- This approach offers a potential solution for safe and effective treatment of triple-negative breast cancer.
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