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PreprintCited by 1Protein Degradation and InhibitorsRNA Interference and Gene DeliveryNanoparticle-Based Drug Delivery

Trim-Away in adult animals through Nano-ERASER and its application in cancer therapy

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Wang, Mingming, Wang, Junfeng, Wang, Yuzhen, Raja, Manikanda, Gupta, Gourab, Hu, Xiangxiang, Shi, Shanshan, Chen, Hexin +2 more·2023·Research Square
DOI 10.21203/rs.3.rs-2298306/v1PMC PMC9882598
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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.

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  • Recently, our group developed a Nano-ERASER system that can downregulate a specific protein by intracellular delivery of its corresponding antibodies via proteasome-mediated degradation, achieving Trim-Away in adult animals and in a disease model for the first time.

    “Recently, our group developed a Nano-ERASER system that can downregulate a specific protein by intracellular delivery of its corresponding antibodies via proteasome-mediated degradation, achieving Trim-Away in adult animals and in a disease model for the first time.”

    From Reverse the progression of Alzheimer’s disease through Nano-ERASER-based adult neuroregeneration (2026) · cites this paper as [20]

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Cited by

Sorted by citations

Authors
Wang, M., Wang, J., Wang, Y., Raja, M., Gupta, G., Hu, X., Shi, S., Chen, H., Fan, D., & Xu, P.
Affiliations
University of South Carolina (US)
ORCID
Venue
Research Square
Publisher
Research Square Platform LLC
Published
2023-01-17
DOI
10.21203/rs.3.rs-2298306/v1
PMC
PMC9882598
OpenAlex
W4316653311
Cited by
0
References
1
Type
posted content
Language
en
Open access
Licence
Locations
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • National Institutes of Health (1r41ag081124-01, 1r01ca263747-01a1)
  • National Cancer Institute (R21CA252360)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
protein degradation, nanogels, PD-L1 inhibitors, triple-negative breast cancer, tumor progression inhibition, cancer immunotherapy

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