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Lipopolyplex Development Service

Introduction Lipopolyplex Workflow What We Can Offer FAQs

Introduction

Creative Biolabs' service focuses on LPP—second-gen non-viral vectors (ternary complexes: polycation-condensed nucleic acid core and lipid bilayer shell) for mRNA/DNA delivery, synergizing polyplex protection and liposome stability to overcome delivery barriers.

It uses advanced multicompartmental LPP technology to ensure superior stability, targeted high-efficiency delivery, precise co-delivery of multiple molecules, and achieves specific synergistic immune programming for next-gen genetic medicines.

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Lipopolyplex Development Service: Mechanism, Application, and Advantages

The LPP system is a powerful, versatile nanocarrier platform designed to enhance the safety and efficacy of genetic medicines.

Mechanism of Enhanced Delivery

  • Targeted Recognition: Tailor the LPP surface chemistry to promote efficient recognition and uptake by APCs (Antigen-Presenting Cells) via macropinocytosis.
  • Endosomal Escape: After internalization, the polymer core's buffering capacity triggers the "proton sponge effect," rupturing the endosome membrane. This step ensures nucleic acids are released into the cytoplasm (protein translation site) before lysosomal degradation.
  • Protein Expression: The liberated mRNA is translated into target antigens or therapeutic proteins, enabling robust, localized immune priming or therapeutic effects.

Diagram of the immune mechanisms of LPP-mRNA vaccine in vivo. (OA Literature)Fig.1 Schematic diagram of the in vivo immune mechanism of LPP-mRNA vaccine.1

Key Applications in Genetic Medicine

The superior customization and control afforded by LPPs make them ideal for complex applications:

  • Personalized Cancer Immunotherapy: Deliver mRNA encoding patient-specific neoantigens, often in synergistic combination with genetic adjuvants, to induce potent CD8+ T cell responses for tumor suppression and recurrence prevention.
  • Gene Replacement Therapy: Achieve high-efficiency delivery of mRNA or DNA plasmids to specific tissue types, enabling transient expression of missing or defective proteins.
  • Vaccinology: Develop next-generation vaccines that require simultaneous presentation of multiple antigens or co-delivery of an immune stimulant.

Workflow

Required Starting Materials

To initiate the service, clients provide:

  1. Nucleic Acid Sequence: Detailed info (e.g., mRNA sequence for tandem neoantigen constructs, DNA plasmid encoding adjuvants).
  2. Target Cell Line: Details of intended cells (e.g., primary Dendritic Cells, DC2.4 murine DC cell line, specific tumor cell line) for in vitro validation.
  3. Desired Formulation Goals: Specific targets for particle size (e.g., 80-150 nm), Zeta potential, and payload ratio (N:P ratio or Lipid: Payload mass ratio).
Consultation & Design
Sequence Optimization

Initial Consultation & Design Engineering

Review client’s payload, target tissue, functional goals; select optimal polymer (e.g., PbAE) and lipid components (e.g., EDOPC/DOPE/DSPE-PEG).

Polyplex Core Assembly & Encapsulation

Cationic polymer complexes with nucleic acid(s) to form a condensed polyplex core; the core is encapsulated in a custom lipid shell.

Chemical Modifications
Synthesis & Purification

Physicochemical Characterization and Optimization

Test via DLS (size/PDI), Zeta potential measurement, TEM (morphology, ~50 nm core detection).

In Vitro Efficacy and Cytotoxicity Testing

Test LPP on client-specified APCs/cell lines; measure transfection efficiency and viability; compare with benchmark systems.

Quality Control & Validation
Delivery & Support

Final Formulation, QC Release, and Reporting

Scale up optimized LPP; conduct comprehensive QC (mRNA integrity, endotoxin testing).

Final Deliverables

  • Detailed LPP Formulation Protocol: Complete manufacturing guide for optimized LPP composition.
  • Physicochemical and QC Report: Docs on size, PDI, Zeta potential, payload EE, stability, and endotoxin levels.
  • In Vitro Transfection and Viability Data: Quantitative results (e.g., gene expression, CC50 values) confirming LPP functionality.
Consultation & Design

What We Can Offer

As an expert in biology, you know that the true challenge in genetic medicine is not sequencing the payload, but successfully delivering it. Creative Biolabs' Custom Lipopolyplex Development Service is your strategic delivery solution, engineered to eliminate the bottlenecks of stability, cell uptake, and endosomal escape.

Full Customization of LPP Architecture

Offer one-stop development with custom selection and tuning of the core-shell structure—including polymer (e.g., PbAE), N:P ratio, lipid composition (e.g., EDOPC/DOPE), and surface PEGylation—to meet requirements of your specific in vivo model or IND pathway.

Guaranteed Precision Stoichiometric Co-Delivery

Use a unique multicompartmental platform to ensure precise, simultaneous co-delivery of dual payloads (e.g., mRNA and plasmid DNA) into the same target cell, providing localized, synergistic signals for effective T cell priming in vaccine development.

Superior Stability and Nuclease Protection

The hybrid core-shell system enhances protection of fragile mRNA and DNA from serum nucleases, extending circulation half-life and ensuring higher-fidelity delivery to intended target cells.

Enhanced APC Targeting and Endosomal Escape

Engineer the LPP surface for high-efficiency uptake by professional Antigen-Presenting Cells (APCs) via macropinocytosis; achieve superior endosomal escape through the polymer core's proton sponge effect.

Comprehensive Quality-by-Design (QbD) Documentation

Each custom LPP batch comes with stringent physicochemical and biological QC reports, validating size, PDI, encapsulation efficiency, and in vitro viability data to enable seamless R&D-to-preclinical transition.

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Customer Reviews

  • [High Transfection Efficacy] "Using Creative Biolabs' Custom Lipopolyplex Development Service in our research has significantly improved mRNA delivery to primary Dendritic Cells, showing a 4× increase in reporter gene expression compared to our previous LNPs, while maintaining minimal cytotoxicity. This allowed us to confirm the TLR 7/8 activation signal was truly vector-intrinsic."

    — R. Smith, [4 Months Ago]

  • [Stoichiometric Co-Delivery] "The ability of Creative Biolabs' LPP to co-deliver our neoantigen mRNA and the GM-CSF plasmid in a 1:1 ratio to the same cell facilitated our study on synergistic immune priming, which was previously impossible using separate, conventional vectors. The precise N:P ratio provided consistent results across all our in vivo studies."

    — A. Cruz, [2 Months Ago]

  • [Superior Stability and QC] "Creative Biolabs' robust physicochemical characterization of our LPP confirmed the core-shell structure integrity via TEM, and the colloidal stability report validated our ability to store the final vaccine product for extended periods—a crucial advantage over the short-lived stability we experienced with our early-stage polyplexes."

    — D. Moore, [7 Months Ago]

FAQs

How does the LPP system compare to a standard Lipid Nanoparticle (LNP) for mRNA delivery?

LPP is a hybrid vector, combining a condensed polyplex core with a lipid shell, while LNPs are typically micelles or vesicles that encapsulate mRNA. LPP's structured core offers superior condensation and protection, and its multicompartmental nature is uniquely suited for stoichiometric co-delivery of two distinct therapeutic payloads (mRNA and plasmid)—a feature often challenging to achieve with high efficiency in simple LNPs.

Can I customize the LPP formulation to target a specific immune cell type?

Yes, absolute customization is a core feature of our service. We can modify the lipid shell composition (including incorporating surface-modifying lipids or targeting moieties, if available) to influence biodistribution and enhance uptake by specific cell populations, such as Dendritic Cells in the spleen or lymph nodes. Our team is ready to discuss your specific targeting requirements.

Why is "stoichiometric control" important for my cancer vaccine project?

Stoichiometric control means the precise, pre-defined ratio of your antigen (mRNA) to your immune adjuvant (e.g., cytokine plasmid) is guaranteed in every LPP particle delivered to the APC. This ensures the cell receives the exact simultaneous signals needed for optimal T cell priming, preventing insufficient or excessive immune activation often seen when these components are delivered separately or non-specifically.

What quality control (QC) measures are included to ensure the safety of the final LPP product?

Our rigorous QC process includes verifying the absence of unencapsulated mRNA, confirming no aggregation via PDI analysis, measuring low endotoxin levels, and performing low-cytotoxicity testing on target cell lines. Final formulations are optimized to be stable and safe for preclinical applications.

The service delivers top-tier engineering control and validated performance in non-viral delivery. It provides superior stability, APC targeting, and unique stoichiometric co-delivery capability, empowering researchers to develop next-generation genetic medicines with enhanced potency and safety.

Contact Our Team for More Information and to Discuss Your Project

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Reference

  1. Fan, Ting, et al. "Lipopolyplex-formulated mRNA cancer vaccine elicits strong neoantigen-specific T cell responses and antitumor activity." Science Advances 10.41 (2024): eadn9961. https://doi.org/10.1126/sciadv.adn9961. Distributed under Open Access license CC BY 4.0, figures were cropped.
All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.