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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.

Advanced Healthcare Materials
|March 30, 2026
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Summary

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.

Keywords:
DNA nanostructureTNBCcGAS‐STINGimmunotherapyinterferon stimulatory DNA

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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.