Trim-Away in adult animals through Nano-ERASER and its application in cancer therapy
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Published on: June 7, 2019
Mingming Wang1, Junfeng Wang2, Yuzhen Wang2
1Department of Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, 715 Sumter, Columbia, SC 29208 (USA).
Abstract:
Trim-Away is a versatile intracellular protein degradation pathway that has been extensively explored in vitro. However, the in vivo application of Trim-Away is limited at oocyte and zygote stages due to the lack of an in vivo practical approach for intracellular antibody delivery. To broaden the application of Trim-Away, especially for clinical use, we developed a nanogel-based Nano-ERASER system. Here, we demonstrated that the intracellular delivery of anti-programmed cell death ligand 1 (PD-L1) antibody through Nano-ERASER could effectively deplete PD-L1 in triple negative breast cancer (TNBC) cells and induce cancer cell death. Furthermore, with the help of a tumor tissue-targeted nanogel, anti-PD-L1 antibody-loaded Nano-ERASER effectively inhibited tumor progression in a TNBC mouse model. These results confirmed that Nano-ERASER realized Trim-Away in adult animals for the first time, which could be an effective tool for disease treatment and studying gene/protein function both in vitro and in vivo.
Insights
Researchers developed Nano-ERASER, a nanogel system, to enable the Trim-Away protein degradation pathway in adult animals. This system effectively targets cancer cells and inhibits tumor growth, offering new therapeutic potential.
Area of Science:
- Molecular Biology
- Biotechnology
- Cancer Research
Background:
- The Trim-Away pathway facilitates intracellular protein degradation but is limited in vivo, especially in adult organisms, due to challenges in delivering antibodies intracellularly.
- Existing methods restrict Trim-Away applications to early developmental stages (oocytes and zygotes), hindering its potential for broader therapeutic and research use.
Approach:
- Developed Nano-ERASER, a novel nanogel-based system for efficient intracellular delivery of antibodies.
- Utilized Nano-ERASER to deliver anti-programmed cell death ligand 1 (PD-L1) antibodies into triple-negative breast cancer (TNBC) cells.
- Incorporated a tumor-targeting nanogel to enhance delivery and efficacy in a TNBC mouse model.
Key Points:
- Nano-ERASER successfully enabled intracellular antibody delivery for Trim-Away in adult animals, a significant advancement.
- Intracellular delivery of anti-PD-L1 antibodies via Nano-ERASER effectively depleted PD-L1 in TNBC cells, inducing cancer cell death.
- The targeted Nano-ERASER system demonstrated significant inhibition of tumor progression in a TNBC mouse model.
Conclusions:
- Nano-ERASER represents the first successful application of Trim-Away in adult animals, overcoming previous delivery limitations.
- This technology holds promise as an effective tool for disease treatment, particularly in cancer therapy.
- Nano-ERASER provides a versatile platform for studying protein function both in vitro and in vivo.
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