LYTACs Design and Development Service
CD ComputaBio provides cutting-edge software-based virtual services to empower researchers, but we do not offer free software packages.
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.
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) |
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| 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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