MNP Custom & CRO Services - Meeting Your Specialized Research Needs

Membrane Protein Nanoparticles (MNPs), a revolutionary platform for membrane protein research, integrate natural cell membranes with nanoparticle technology to provide unprecedented solutions for drug discovery, antibody development, and structural biology studies. We understand that every research project is unique, which is why we offer comprehensive custom development and CRO services to ensure your specialized research needs are met with precision.

MNP Custom Service Scope

New Target Development: MNP Preparation for Membrane Proteins Not on Our List

We provide complete development services from scratch for innovative membrane protein targets that are not yet commercially available or have limited literature reports. Our technical team possesses extensive experience in membrane protein expression and purification, covering complex targets such as G protein-coupled receptors (GPCRs), ion channels, transporters, and immune checkpoint proteins.

Service Workflow Includes:

• Gene Optimization & Synthesis: Codon optimization based on host cell preferences to enhance expression efficiency
• Expression System Screening: Testing optimal expression strategies in mammalian cells (HEK293, CHO), insect cells (Sf9, Hi5), or yeast systems
• Membrane Protein Extraction & Purification: Employing detergent screening, nanodisc reconstitution, or direct membrane preparation techniques
• MNP Preparation & Characterization: Enrichment of membrane components via ultracentrifugation and density gradient centrifugation; dynamic light scattering (DLS) verification of uniform particle size (typically 50-200 nm); Western blot confirmation of target protein integration efficiency
• Functional Validation: Ligand binding assays, surface plasmon resonance (SPR), etc., to ensure protein activity

Delivery Standards: Particle concentration ≥1 mg/mL, protein integration rate >70%, activity retention >85%, with a complete QC data package.

Special Species: Mouse, Rat, and Monkey Orthologous Protein MNPs

Cross-species studies are crucial in drug safety evaluation and translational medicine. We have successfully built a multi-species orthologous protein MNP library to support your preclinical research needs.

Technical Features:

• Sequence Homology Analysis: Comparing protein sequences across different species to predict potential antigenic epitope differences
• Species-Specific Preparation: Extracting membrane components from primary tissues or transfected cells of mouse (C57BL/6), rat (SD), or cynomolgus monkey (Macaca fascicularis)
• Immunogenicity Assessment: Comparing cross-reactivity of different species MNPs with candidate antibodies via ELISA
• Toxicology-Relevant: Particularly suitable for off-target toxicity screening of ADC drugs and bispecific antibodies

Application Scenarios: Cross-reactivity testing of antibodies, preclinical efficacy studies in animal models, species-specific epitope mapping, and species comparison data required for FDA/NMPA submissions.

Mutants/Truncates: Investigating Specific Domain Functions

Precisely dissecting protein functional domains is central to drug mechanism studies. We offer rationally designed mutant and truncate MNP preparation services.

Customization Types:

• Point Mutations: Introduction of single amino acid mutations (e.g., phosphorylation sites, key ligand-binding residues)
• Truncation Mutants: Deletion of specific domains (e.g., intracellular domains, extracellular loop regions)
• Chimeric Constructs: Cross-protein domain swapping to investigate modular functions
• Tag Insertions: Insertion of FLAG, HA, His, etc., tags at specific sites

Quality Control: Each mutant undergoes sequencing verification, expression level confirmation, and functional comparison testing to ensure mutations do not affect particle stability. Parallel comparison data between mutants and wild-type are provided to help you accurately interpret experimental results.

Labeling Customization: Fluorescent Labeling, Biotinylation, Magnetic Bead Conjugation

To meet diverse detection needs, we offer multiple chemical modification services that preserve MNP native conformation while enhancing detection sensitivity.

Labeling Options:

• Fluorescent Labeling: Alexa Fluor 488/647, CFSE, DiR, etc., for flow cytometry (FACS), confocal imaging, and in vivo tracking. Labeling efficiency >90%, fluorescent signal stable for over 4 weeks
• Biotinylation: Using NHS-biotin or cleavable biotin labeling, suitable for immunoprecipitation (pull-down), SPR/BLI detection. Controllable labeling density (5-50 biotin molecules per particle)
• Magnetic Bead Conjugation: Covalent coupling of MNPs to carboxyl/amino magnetic beads (1-5 μm) for rapid separation and enrichment, applicable for cell sorting and co-immunoprecipitation
• Isotope Labeling: ³H or ¹⁴C labeling for quantitative pharmacokinetic studies

Optimization Strategy: Labeling conditions are optimized via DOE (Design of Experiments) to ensure labeling does not affect protein activity, with unlabeled and labeled control groups provided for background subtraction.

2. CRO Technical Service Packages

Antibody Screening Services: Hybridoma Screening, Phage Library Screening

Based on the high antigen presentation efficiency of MNPs, we provide rapid, high-success-rate antibody discovery CRO services.

Hybridoma Screening:

• MNP immunization of Balb/c mice to overcome the bottleneck of weak immunogenicity from traditional cell immunization
• Standard 8-week immunization cycle capable of producing 10⁶-10⁷ splenocytes
• Multi-round screening: ELISA binding screening (excluding particle scaffold interference), flow cytometry screening (recognizing native conformational epitopes), functional screening (blocking/activation assays)
• Deliverables: 5-10 positive clones, antibody sequences, 10 mg purified antibody, affinity (KD) determination report

Phage Display Screening:

• Providing naïve or immune-source (MNP-immunized) phage libraries
• Solid-phase/liquid-phase screening strategies with negative selection to exclude non-specific binding
• Obtaining 10²-10³ positive clones after 3-4 rounds of panning
• Deep Analysis: NGS sequencing to analyze enrichment trajectories and predict affinity maturation pathways

Advantages: MNPs maintain native membrane protein conformation, significantly increasing the proportion of antibodies recognizing conformational epitopes (from <5% with traditional methods to >30%).

Compound Screening Services: HTS, LEAD Optimization

Providing MNP-based compound screening solutions for difficult-to-drug targets.

High-Throughput Screening (HTS):

• Screening Libraries: Diversity libraries (50,000-500,000 compounds), AI-designed targeted libraries, fragment libraries available
• Detection Platforms: HTRF, AlphaScreen, FLIPR (GPCR calcium flux), SPR high-throughput versions
• Throughput: Daily screening capacity of 10,000-50,000 compounds
• Data Quality: Z' factor >0.5, complete dose-response curves provided

Lead Optimization (LEAD Optimization):

• Structure Guidance: Designing focused compound libraries based on Cryo-EM or homology modeling
• AIDD/CADD: AI molecule generation, free energy perturbation (FEP) predictions
• ADMET Prediction: Early-stage druggability assessment to reduce late-stage failure risk
• Iteration Cycle: SAR analysis reports provided within 2-4 weeks

Specialized Service: Inhibitor screening for efflux transporters such as P-gp and BCRP, using MNPs to reconstruct unidirectional transport functions that more authentically reflect in vivo conditions.

Structural Determination Services: Cryo-EM Sample Preparation, Negative Stain EM

MNPs serve as an ideal "soluble membrane protein" format, greatly simplifying structural biology studies.

Cryo-EM Sample Preparation:

• Sample Optimization: Particle size homogenization, detergent screening, cryoprotectant optimization
• Grid Preparation: Quantifoil/Au 300/400 mesh grids, ice thickness control (50-100 nm)
• Data Collection: 200-300 kV field emission cryo-electron microscopy with automated data collection
• Data Processing: 2D classification, 3D reconstruction, atomic model building
• Deliverables: 2-4 Å resolution structure (depending on protein characteristics), raw data, processing workflow

Negative Stain EM (Rapid QC):

• Low-resolution structure (15-20 Å) provided within 2 weeks
• Verification of correct MNP assembly and protein integration orientation
• Suitable for early-stage go/no-go decision making

Unique Advantages: MNPs eliminate the impact of traditional detergents on protein structure, enabling capture of membrane protein conformations in native lipid environments. Successful cases include GLP-1R-GPCR complexes and TRPV1 ion channel structures.

Functional Validation Services: Cell Signaling, Animal Studies

Bridging in vitro and in vivo research to provide complete functional validation data.

Cell-Level Validation:

• Signaling Pathway Detection: cAMP, IP-One, ERK phosphorylation, Ca²⁺ flux kinetics
• Reporter Gene Systems: NF-κB, AP-1, SRE-driven luciferase reporter systems
• Cell Binding Assays: FACS detection of antibody/compound binding to overexpressing cells
• Internalization Assays: pH-sensitive fluorescent labeling to track MNP-ligand complex endocytosis pathways

Animal Model Services:

• Efficacy Evaluation: Pretreatment with orthologous MNPs to block antibody efficacy (neutralization experiments)
• PK/PD Studies: Radiolabeled or fluorescently labeled MNPs to evaluate in vivo distribution
• Immunogenicity Assessment: Antibody titer monitoring using MNPs as immunogens
• Disease Models: Using orthologous MNPs in humanized mouse models to simulate pathological states

Compliance: Animal studies conducted in AAALAC-accredited facilities following 3R principles, with complete IACUC approval documentation provided.

Project Management & Delivery

Dedicated Project Manager Responsibility System

Each project is assigned an experienced project manager as the single client contact to ensure smooth communication.

Responsibilities Include:

• Project Kickoff Meeting: Deep understanding of client needs and development of detailed work plans
• Resource Coordination: Allocation of technical teams, equipment, and raw materials
• Risk Management: Identification of technical risks and development of contingency plans
• Quality Control: Supervision of experimental protocol compliance and data accuracy review
• Client Relations: Regular follow-ups, feedback collection, and continuous improvement

Biweekly Progress Reporting

Reporting Format: conference + written report

Content Coverage:

• Work Progress: Completed experiments, key data
• Issues & Challenges: Technical difficulties, deviation analysis
• Next Phase Plan: Specific experimental arrangements, expected outcomes
• Decision Points: Critical nodes requiring client confirmation (e.g., candidate molecule selection)

Report Template: Standardized template ensures completeness, customizable per client preference.

Phased Data Delivery

Data Transparency: Raw data, processed data, and preliminary analysis delivered within 3 business days of milestone completion.

Data Package Includes:

• Electronic lab notebook
• Instrument raw files
• Statistical analysis code
• Certificate of Analysis (COA)

Data Portal: Clients can access real-time cloud data via dedicated VPN to monitor project progress anytime.

Detailed Technical Report & Protocol Transfer

Comprehensive Technical Report (TRS) delivered at project completion, including:

• Executive Summary: Project objectives, methods, key results, conclusions
• Materials & Methods: Detailed experimental protocols (reproducible), reagent lists (with catalog numbers), instrument parameters
• Results: Illustrated data presentation, statistical analysis, QC standards
• Discussion: Result interpretation, limitation analysis, future recommendations
• Appendices: Raw data, primer sequences, plasmid maps

Protocol Transfer: SOPs provided in electronic format with training videos; on-site demonstrations available for critical steps to ensure smooth technology transfer to client teams.

Post-Project Support: Free consultation services for 6 months after project completion, assisting in publication and patent application material preparation.

Contact us today to accelerate your research breakthroughs with our MNP custom development and CRO services! We are committed to being your trusted R&D partner with the highest quality standards, most flexible collaboration models, and most transparent project management.