# Chemical Glycobiology Tool Development: LYTACs

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $13,393

## Abstract

Project Abstract
Lysosome targeted chimeras (LYTACs) are a recently developed technology that enable targeted
internalization and subsequent degradation of a cell surface antigen by engaging the cation- independent
mannose-6-phosphate receptor (CI-M6PR). The modular design of LYTACs enable its implementation in
other therapeutic antibody-based modalities including antibody-drug conjugates (ADCs). We will develop
ADC/LYTACs, which consist of an ADC conjugated to CI-M6PR binding ligands, which will provide a
supplemental internalization and efficient lysosomal trafficking route independent of the inherent
characteristics of a tumor antigen. To reduce off-target cytotoxicity, the CI- M6PR binder will be carefully
optimized and a two-component strategy will be tested where the tumor antigen is pre-treated by a non-
internalizing ADC before clicking on the internalizing ligand in vitro. Further, prodrug analogues of the CI-
M6PR ligand will be developed to enhance the pharmacokinetic properties of this new therapeutic
modality. We envision that ADC/LYTACs will significantly expand the target space for ADCs to include
highly specific yet poorly internalizing tumor antigens.

## Key facts

- **NIH application ID:** 10809225
- **Project number:** 3R01GM058867-25S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Carolyn Bertozzi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $13,393
- **Award type:** 3
- **Project period:** 1999-01-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809225

## Citation

> US National Institutes of Health, RePORTER application 10809225, Chemical Glycobiology Tool Development: LYTACs (3R01GM058867-25S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10809225. Licensed CC0.

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