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mRNA Lipopolyplex Delivery Development

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Creative Biolabs leverages cutting-edge Lipopolyplex (LPP) nanotechnology to overcome mRNA delivery challenges in preclinical research. Our platform integrates lipid-polymer hybrid nanoparticles to protect mRNA, enhance cellular uptake, and enable tissue-specific targeting—all tailored to accelerate your in vitro and in vivo studies.

Technology Overview: The LPP Advantage

  • LPP combines cationic lipids, polymers, and mRNA into stable, multilayered nanoparticles:
  • Core-shell architecture: Polymeric core condenses mRNA, while lipid shell fuses with cell membranes for efficient cytosolic release.
  • Dual functionalization: Customizable with targeting ligands (e.g., peptides, antibodies) and immune modulators (e.g., Mn²⁺ adjuvant) to direct organ/cell selectivity and amplify immune responses.
  • Enhanced biocompatibility: Reduced cytotoxicity compared to traditional LNPs, validated in primary immune cells and epithelial models.

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mRNA LPP Delivery Development

Creative Biolabs' Lipopolyplex (LPP) Platform provides modular nanotechnology solutions for preclinical mRNA delivery research. By integrating programmable lipid-polymer hybrids with rational design principles, we enable researchers to:

Fig.1 LPP Delivery Development Service Highlights. (Creative Biolabs Authorized)Fig.1 LPP Delivery Development Service Highlights.

Mechanism-Driven Formulation Design Services

Targeting Strategy Exploration:

  • UTR/Ligand Screening: Screen UTR element/ligand libraries to identify cell-specific sequences/moieties.
  • Biodistribution Analysis: Provide quantitative real-time trafficking using fluorescent/radioactive tags.

High-Purity mRNA Preparation:

  • dsRNA Elimination: Implement protocols to minimize unintended immune activation.
  • Extended Expression Windows: Enable long-duration protein expression kinetics studies.

Disease Mechanism Profiling Services

Adaptive Immune Response Analysis:

  • Antigen Presentation Profiling: Analyze MHC-I/II pathway activation mechanisms.
  • Germinal Center Monitoring: Track germinal center formation and B cell maturation.
  • Tissue-Resident Immunity Dynamics: Characterize induction and function of tissue-resident immune cells.

Onco-Microenvironment Mechanistic Investigation:

  • Neoantigen-Specific T Cell Priming: Investigate priming mechanisms.
  • Immune Checkpoint Function Analysis: Assess mRNA payload effects on checkpoint molecules.

Translational Research Tool Services

LNP Characterization:

  • Size/PDI/Zeta Potential: Measure core parameters & correlate with cellular uptake.
  • mRNA Release Kinetics: Quantify release rates under physiological conditions (in vitro).
  • Serum Stability: Evaluate stability and payload protection in serum (in vitro).

Research-Grade LNP Production:

  • High Batch Consistency: Ensure intra-batch particle uniformity for reliable studies.
  • Custom Surface Engineering: Provide PEGylation, ligand conjugation, etc.

Related mRNA Services

Lipid-based Vector Development

  • LNP Development: mRNA encapsulation & cell-targeted delivery
  • Targeted LNPs: Receptor-specific cellular uptake
  • Liposome Systems: Serum-stable mRNA complexation

Polymer-based Vector Development

  • Polyplexes: Endosomal escape enhancement
  • Micelleplexes: Sustained mRNA release
  • Biodegradable polymers: Low cytotoxicity designs

Hybrid Vector Development

  • Lipopolyplexes: Lipid-polymer stability synergy
  • Cationic Nanoemulsions: High mRNA payload delivery
  • Hybrid optimization: Tailored transfection efficiency

eVLP Development

  • LVLPs: Broad-tropism single-cycle transduction
  • MLVLPs: High-titer immune cell delivery
  • VEEVLPs: Rapid cytoplasmic mRNA release

Emerging Research Applications for LPP Technology

1. Photo-responsive Gene Activation Systems

Using LPPs decorated with photosensitizers (e.g., hypericin) in photochemical strategies has been shown to enable light-triggered cytosolic nucleic acid release via ROS-mediated endosomal disruption. This approach can enable spatial and temporal control of gene expression in vitro with higher transfection efficiency in hepatocellular carcinoma models compared to PEI-based vectors while reducing cytotoxicity. It can serve as a precision tool for investigating endosomal escape kinetics and stimulus-responsive delivery mechanisms.

2. Modular Vaccine Research Platforms

Mucosal administration (e.g., via airway) of LPPs modified for tissue-resident delivery can elicit sIgA and tissue-resident memory T cells (TRM) to combat respiratory infections like RSV. Delivering mRNA antigens together with immune potentiators (e.g., Mn2+) enables investigators to probe the role of cGAS-STING pathway activation and its relationship with T-cell clonal expansion in tumor models, which will serve as a standardized system for probing adaptive immunity mechanisms.

3. Advanced CNS Delivery & Gene Editing

Peptide modification of LPPs (e.g., TfR1-targeting variants) enables receptor-mediated transcytosis across in vitro blood-brain barriers to deliver gene-editing reagents (e.g., CRISPR-Cas9 RNP) to neuronal cells. On the other hand, mitochondria-targeted LPPs exploit electrochemical gradient-responsive lipids to probe heteroplasmic mutation correction mechanisms in mitochondrial diseases to advance subcellular delivery research.

4. Tumor Microenvironment Remodeling

Surface modification of LPPs (e.g., RGD peptide conjugation) to deliver a combinatorial payload (mRNA + STING agonist) to investigate dendritic cell maturation kinetics and cytotoxic T lymphocyte trafficking patterns in metastatic models, which enables immune checkpoint modulation without any therapeutic claims to focus on the crosstalk between tumor and immune system. Cationic polymers electrostatically interact with anionic nucleic acids (DNA, mRNA, siRNA) to form polyplex nanocomplexes that protect genetic materials from enzymatic degradation and improve cellular uptake. Polyplexes have higher stability and tunable surface properties compared to lipoplexes and can encapsulate stimulus-responsive materials for the controlled release inside cells.

Key Technological Advances

Application Core Innovation Research Value
Photo-controlled Delivery Light-triggered endosomal disruption Spatiotemporal precision for gene circuit studies
Mucosal Immunity Platform TLR agonist-enhanced APC activation Modeling natural infection immune responses
CNS-Targeted Editing Receptor-mediated transcytosis optimization BBB penetration mechanism analysis
Tumor Immune Modulation Combinatorial immune potentiator co-delivery Tumor-immune synapse deconvolution

Published Data

This study systematically evaluates mRNA lipoplexes prepared via modified ethanol injection (MEI). Screening 18 formulations with varied cationic lipids (including DC-1-16/TC-1-12), helper lipids, and PEG-Cholesterol, researchers identified DC-1-16/DOPE/PEG-Chol as optimal. This formulation demonstrated:

  • Enhanced transfection efficiency – Robust protein expression in vitro and in vivo;
  • Organ-specific delivery – Significant protein production in murine lungs/spleen;
  • Immunogenicity – Induced high antigen-specific IgG1 titers post-immunization.

The MEI method proves effective for developing mRNA delivery systems with improved translational capacity.

Fig.2 mRNA biodistribution and protein expression in mice after IM injection of mRNA lipoplexes. (OA Literature)Fig.2 mRNA biodistribution and protein expression in mice after IM injection of mRNA lipoplexes.3

Partner with Creative Biolabs

Leverage 15+ years of nucleic acid nanotechnology expertise to advance your preclinical mRNA research. Our specialized LPP development platform delivers:

  • Targeting Mechanism Mastery: Proprietary ligand screening platforms and tissue-optimized UTR libraries for precise expression control in research systems
  • End-to-End Discovery Support: Integrated workflows from sequence design through in vivo PK/PD relationship studies
  • Dedicated Research Compliance: All programs strictly adhere to preclinical standards—exclusively for non-clinical investigation

Precision LPP Development for Transformative Research

Creative Biolabs pioneers end-to-end lipopolyplex development services that merge advanced polymer-lipid hybridization with targeted delivery engineering. Our platform enables researchers to overcome nucleic acid delivery barriers through customizable LPP architectures optimized for specific biological challenges, whether exploring CNS-targeted gene editing tools, dissecting tumor-immune interactions via co-delivery systems, or developing stimuli-responsive vectors for spatial control of gene expression. By integrating rational design principles with AI-accelerated formulation screening, we deliver non-viral solutions with enhanced tissue tropism and reduced off-target effects, exclusively for preclinical validation.

Initiate Your Project Today

Partner with our nucleic acid specialists to design a bespoke LPP development strategy. Share your target tissue, payload specifications, and validation requirements to receive a feasibility assessment. For technical documentation or case studies, contact our team directly for scientific consultation.

FAQs

Q1: How does LPP technology differ from conventional LNPs in research applications?

A: LPP's lipid-polymer hybrid architecture enables superior endosomal escape and non-hepatic tissue targeting, making it particularly valuable for studying immune cell transfection mechanisms and organ-specific delivery biology.

Q2: What measures ensure functional mRNA delivery in experimental systems?

A: We implement dsRNA removal protocols, tissue-optimized UTR designs, and low-temperature formulation processes to maintain mRNA integrity and expression kinetics throughout preclinical studies.

Q3: Can LPPs be customized for specialized cell types like neurons or T cells?

A: Yes, our ligand-screening platforms support tailored surface functionalization and charge optimization for cell-type-specific delivery, validated through primary cell transfection and tissue distribution studies.

Q4: Is co-delivery of CRISPR components feasible with your LPP system?

A: We enable Cas9 mRNA/sgRNA co-encapsulation for gene editing research in cellular and organoid models, with comprehensive off-target effect analysis guidance.

Q5: How is batch consistency maintained?

A: Standardized microfluidic synthesis and rigorous physicochemical characterization ensure reproducible nanoparticle properties suitable for longitudinal research.

Q6: What is the typical project timeline?

A: From design to data delivery, most projects progress through formulation optimization, in vitro validation, and optional animal studies within a multi-week framework.

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References

  1. Shah, Hirva, et al. "In Vitro Photoselective Gene Transfection of Hepatocellular Carcinoma Cells with Hypericin Lipopolyplexes." ACS Applied Materials & Interfaces 16.33 (2024): 43416-43429. Distributed under Open Access license CC-BY-NC-ND 4.0, without modification. https://doi.org/10.1021/acsami.4c10438
  2. Zhang, Fengrong, et al. "Chemical-electron-transfer-based lipopolyplexes for enhanced siRNA delivery." Cell Reports Physical Science 4.6 (2023). Distributed under Open Access license CC-BY-NC-ND 4.0, without modification. https://doi.org/10.1016/j.xcrp.2023.101444
  3. Tang, Min, et al. "Efficient mRNA delivery with mRNA lipoplexes prepared using a modified ethanol injection method." Pharmaceutics 15.4 (2023): 1141. Distributed under Open Access license CC-BY 4.0, without modification. https://doi.org/10.3390/pharmaceutics15041141
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