LYTACs Design and Development Service

Our service provides end-to-end solutions for creating lysosome-targeting chimaeras (LYTACs)-a groundbreaking therapeutic strategy that expands targeted protein degradation beyond intracellular proteins. Using advanced computational design, bioconjugation chemistry, and receptor biology expertise, we engineer bifunctional molecules that couple disease-related extracellular or membrane proteins to lysosomal trafficking receptors (LTRs), enabling their selective internalization and degradation. Our platform empowers researchers to target previously "undruggable" extracellular proteins, antibodies, or receptors with high specificity and minimal off-target toxicity.

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Core Capabilities

Computational Ligand and Linker Design
- Structure-guided design and molecular docking to identify optimal binding pairs for the target protein and LTR (e.g., CI-M6PR, ASGPR).
- In silico linker optimization for stability and spatial flexibility.
Receptor-Ligand Engineering
- Screening and modification of lysosomal targeting ligands (mannose-6-phosphate, GalNAc derivatives, etc.).
- Affinity optimization for effective trafficking and endocytosis.
Bioconjugation Chemistry
- Chemical synthesis and conjugation of the target-binding moiety with lysosomal targeting ligands using click chemistry, PEG linkers, or bio-orthogonal methods.
- Purity validation and structural confirmation (HPLC, MS).
Cell-Based Internalization & Degradation Assays
- Quantify target degradation via western blot, ELISA, or flow cytometry.
- Track trafficking to lysosomes using live-cell imaging and fluorescence labeling.
Pharmacokinetic & Stability Evaluation
- In vitro and in vitro stability profiling.
- Assessment of tissue distribution and degradation efficiency.

Applications

Area	Applications
Therapeutic Protein Degradation	Elimination of disease-associated extracellular or membrane proteins.
Oncology & Immunotherapy	Degradation of growth factors, immune checkpoints, and tumor antigens.
Neurodegenerative Diseases	Clearance of extracellular aggregates (e.g., tau, α-synuclein).
Autoimmune Disorders	Targeting overactive cytokines or receptors to modulate immune response.
Antibody and Receptor Target Validation	Evaluate degradation feasibility for therapeutic antibody targets.

Key Advantages

Targets extracellular and membrane-bound proteins beyond Proteolysis-targeting Chimera scope.
Compatible with a variety of ligand–linker architectures.
Customizable for different lysosomal receptors (CI-M6PR, ASGPR, Sortilin).
Reduced off-target effects via receptor-specific internalization.
Accelerates drug discovery for challenging targets.

Deliverables

Designed and synthesized LYTACs candidates.
Structural and biophysical characterization data.
In vitro degradation and trafficking validation reports.
Optional in vivo proof-of-concept study.

Comparison of Targeted Protein Degradation Platforms

Feature	Lysosome-Targeting Chimeras	Cytokine-based Targeting Chimeras	Proteolysis Targeting Chimeras
Primary Target Space	Extracellular and membrane-bound proteins	Extracellular and membrane-bound proteins	Intracellular proteins
Mechanism of Action	Utilizes lysosome-shuttling receptors (e.g., CI-M6PR, ASGPR) to transport target proteins for lysosomal degradation	Leverages cytokine receptor-mediated endocytosis to internalize and degrade target proteins via lysosomal pathways	Uses E3 ubiquitin ligase recruitment to mark target proteins for proteasomal degradation
Molecular Architecture	Bifunctional molecule linking target binder (antibody/small molecule) to lysosomal receptor ligand	Cytokine–antibody fusion protein that binds both target and cytokine receptor	Bifunctional small molecule linking target ligand to E3 ligase ligand
Uptake Pathway	Lysosomal receptor-mediated endocytosis	Cytokine receptor internalization (e.g., IL-2R, GM-CSFR)	Intracellular ubiquitin–proteasome system
Subcellular Destination	Lysosome	Lysosome	Proteasome
Target Classes	Membrane receptors, secreted proteins	Membrane receptors, secreted cytokines, extracellular enzymes	Transcription factors, kinases, enzymes
Molecule Type	Large biologic or conjugate (~100–200 kDa)	Large biologic (~100–150 kDa fusion protein)	Small molecule (<1 kDa)
Design Complexity	Moderate to high (ligand–receptor pair matching, linker optimization)	Moderate (cytokine–antibody fusion, linker engineering)	High (ligase selection, linker optimization, cell permeability)
Selectivity & Tunability	High selectivity; dependent on receptor expression	High selectivity; tunable cytokine activity and receptor choice	Dependent on E3 ligase expression and target engagement
Delivery Requirements	Protein or conjugate delivery (IV)	Protein therapeutic delivery (IV or SC)	Cell-permeable small molecule delivery (oral or IV)
Advantages	Expands degradation to non-internalizing extracellular targets	Utilizes native cytokine pathways for internalization	Well-established technology
	Modular design using known lysosomal receptors	No lysosomal receptor dependency	High intracellular efficiency
		Enables extracellular target degradation	Reversible and catalytic mechanism
Limitations	Restricted by receptor expression profile	Limited to cells expressing cytokine receptors	Limited to intracellular proteins
Limitations	Complex conjugate synthesis	Requires careful cytokine tuning to minimize off-target signaling	Potential off-target ubiquitination
Stage of Development	Emerging (preclinical validation)	Emerging (preclinical proof-of-concept)	Established (multiple clinical candidates)

Why Choose Us

Our multidisciplinary team integrates computational chemistry, protein engineering, and receptor biology to deliver fully customized LYTACs molecules from concept to validation. By combining rational design and experimental screening, we help accelerate the development of next-generation therapeutics targeting the extracellular degradome.

* For Research Use Only.

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