Intracellular delivery
Cell-Penetrating Peptide Design for Intracellular Delivery
Cell-penetrating peptides are a critical enabling technology for delivering therapeutic cargo — nucleic acids, proteins, small molecules — across the plasma membrane. Designing CPPs with the right uptake efficiency, endosomal escape, and cell-type selectivity requires precise sequence engineering. We apply computational methods to design and optimize CPPs for your specific delivery application.
The Intracellular Delivery Challenge
The plasma membrane is an effective barrier against most therapeutic molecules. Nucleic acids, proteins, and many small molecules cannot cross the membrane unaided, limiting their therapeutic utility. Cell-penetrating peptides offer a sequence-defined solution — but designing CPPs with sufficient uptake efficiency, endosomal escape, and acceptable toxicity requires careful optimization.
Computational methods that model membrane interaction, predict uptake efficiency, and optimize CPP sequences for specific cargo and cell types can significantly accelerate CPP development and reduce the experimental burden of empirical screening.
Our CPP Design Approach
Uptake mechanism classification
Computational classification of CPP uptake mechanism — direct translocation vs. endocytosis — to guide sequence design for the target application.
Amphipathicity and charge optimization
Optimization of the amphipathic helix structure and cationic charge distribution for membrane interaction and uptake efficiency.
Endosomal escape engineering
Design of pH-responsive or membrane-disruptive elements to improve endosomal escape for endocytosis-dependent CPPs.
Cargo compatibility assessment
Evaluation of CPP-cargo conjugation strategies and their effect on uptake efficiency and intracellular trafficking.
CPP Design Workflow
Application and cargo definition
Define the cargo, target cell type, and intracellular destination.
CPP class selection
Computational assessment of CPP classes (cationic, amphipathic, hydrophobic) for the application.
Sequence design and optimization
AI-assisted generation of CPP sequences optimized for uptake, endosomal escape, and cargo compatibility.
Property prediction
Prediction of membrane permeability, uptake efficiency, cytotoxicity, and stability.
Candidate prioritization
Selection of priority CPP candidates for synthesis and experimental validation.
Optimization cycles
Iterative refinement based on experimental uptake and toxicity data.
What Can Be Evaluated
What You May Receive
CPP candidate library
Designed CPP sequences with predicted uptake efficiency, endosomal escape, and toxicity profiles.
CPP class analysis
Assessment of CPP class options and rationale for the selected approach.
Cargo conjugation strategy
Recommended conjugation approaches and their predicted effect on uptake and intracellular trafficking.
Optimization strategy
Recommended modifications to improve uptake efficiency, endosomal escape, or reduce toxicity.
Deliverables depend on project scope and cargo type. Uptake efficiency and endosomal escape outcomes cannot be guaranteed computationally.
Who This Is For
Nucleic acid delivery programs
Teams developing siRNA, mRNA, or antisense oligonucleotide therapeutics that require intracellular delivery vectors.
Protein delivery applications
Programs delivering therapeutic proteins, antibody fragments, or CRISPR components intracellularly.
Drug discovery groups
Teams targeting intracellular proteins with peptide or small molecule cargoes that require membrane-crossing delivery.
Screen Your CPP Candidate
Use our free tools to assess the physicochemical properties of your CPP candidate. Net charge at pH 7.4 and GRAVY score — calculated by the Peptide Property Analyzer — are key indicators of CPP uptake potential. The Drug-Likeness Predictor estimates membrane permeability.
Frequently Asked Questions
Design CPPs for Your Intracellular Delivery Application
Submit your cargo type, target cell type, and delivery requirements. We will assess the CPP design opportunity and outline a computational approach for your program.
Confidential project discussions available under NDA.