Developing mRNA therapeutics that target specific immune cell subsets in vivo requires delivery systems that protect the mRNA, mediate cellular uptake, and minimize off-target accumulation. Our Custom mRNA Delivery System Development service provides end-to-end support—from formulation design through preclinical characterization—to help you select the optimal carrier for your in vivo cell therapy candidate.
We work with your mRNA sequence to formulate lipid nanoparticles (LNPs) and other delivery vehicles that are optimized for encapsulation efficiency, particle size, polydispersity, and stability. Each formulation is then evaluated in vitro for cellular uptake and cytotoxicity, followed by in vivo biodistribution and immunogenicity studies in relevant preclinical models. Our integrated workflow enables iterative optimization so that the lead delivery system meets your target product profile.
Whether your goal is to deliver mRNA to T cells, NK cells, dendritic cells, or other immune populations, our team of formulation scientists and in vivo pharmacologists brings deep expertise in nucleic acid delivery and preclinical study design to your program.
Key Features
Custom LNP Formulation & Scale-Up
We design and manufacture lipid nanoparticles (LNPs) with tunable lipid compositions that optimize encapsulation efficiency and particle characteristics. Formulations are prepared using microfluidic mixing or thin-film hydration, and we can incorporate targeting ligands (e.g., antibodies, peptides) for cell-specific uptake. Scale-up quantities for in vivo studies are provided at matched quality.
Particle Characterization & Stability Testing
Each formulation is characterized for particle size (dynamic light scattering), polydispersity index, zeta potential, and encapsulation efficiency (RiboGreen assay). Stability is assessed under relevant storage conditions (e.g., 4°C, -20°C, -80°C) over time, including assessment of integrity by agarose gel or RT-qPCR.
In Vitro Uptake & Cytotoxicity Assays
We evaluate formulation performance in relevant immune cell lines or primary cells. Assays include flow cytometry-based uptake quantification (fluorescently labeled mRNA or dye-loaded LNPs), cell viability (MTS, LDH release), and early markers of activation (e.g., CD69, CD25). Results guide lead selection before in vivo testing.
In Vivo Biodistribution, Immunogenicity & Tolerability
In vivo studies are performed in mice (and, when scoped, rats) to determine organ and tissue distribution of the mRNA or carrier (biodistribution by qRT-PCR, BLI, or fluorescent imaging). Immunogenicity is assessed via serum cytokine profiling (MSD, ELISA), anti-carrier antibody titers, and local injection-site histopathology. Tolerability includes clinical scoring, body weight, and clinical chemistry.
Delivery System Modalities
Our service is compatible with a range of carrier platforms, selected based on your target cell type and therapeutic application.
Ionizable Lipid Nanoparticles (LNPs): The most widely used platform for mRNA delivery. We tune the ionizable lipid, helper lipids, cholesterol, and PEG-lipid ratios to achieve high encapsulation and endosomal escape, with optional targeting moieties.
PEGylated LNPs for Long Circulation: Formulations with optimized PEG-lipid content to reduce rapid clearance and improve accumulation at target tissues, particularly useful for intravenous administration.
Lipid-Polymer Hybrid Nanoparticles: Combination carriers that merge the stability of polymers (e.g., PLGA) with the endosomal escape properties of lipids, offering controlled release and enhanced payload protection.
Cationic Lipid-Based Carriers (Lipoplexes): Simpler formulations where cationic lipids are complexed directly with mRNA. Useful for rapid in vitro screening or local administration (e.g., intratumoral).
Cell-Specific Targeting Decorations: We can incorporate antibodies or receptor-binding peptides onto the carrier surface to direct delivery to specific immune cell subsets (e.g., CD4+ T cells, NK cells).
Workflow
Our integrated workflow combines formulation, characterization, and preclinical evaluation, with each step optimized for reproducibility and decision-making.
Project Scoping & Design: We discuss your mRNA cargo, target cell type, route of administration, and desired product profile. Together we define the carrier platform(s) to test, analytical endpoints, and study parameters.
Formulation Development & Characterization: Our formulation team prepares candidate LNPs or alternative carriers with specified lipid/polymer compositions. Each batch is characterized for size, PDI, zeta potential, encapsulation efficiency, and stability.
In Vitro Screening: Lead formulations are tested in relevant immune cell lines or primary cells for uptake efficiency, cytotoxicity, and functional mRNA expression (e.g., reporter or therapeutic protein). Results narrow candidates for in vivo assessment.
In Vivo Biodistribution & Immunogenicity: Selected candidates are administered in rodent models. We quantify mRNA distribution (by qRT-PCR or BLI), assess anti-carrier immune responses, and evaluate local and systemic tolerability.
Data Analysis, Reporting & Iteration: All raw data, analytical methods, and study results are compiled in a comprehensive report. We discuss next steps—whether to proceed with a lead candidate, refine the formulation further, or expand to additional models.
Iterative Optimization
Our workflow includes iterative optimization built into every stage, from formulation through in vivo readout, so the lead delivery system is data-driven rather than assumption-driven.
Quality Assurance
All formulation and assay steps follow written standard operating procedures (SOPs). Particle characterization instruments are calibrated regularly, and in vitro / in vivo studies include appropriate controls (e.g., empty carriers, buffer-only, positive controls). Data are reviewed by independent scientists before release.
For in vivo studies, we adhere to accredited animal care standards (where applicable) and IACUC-approved protocols. We provide full documentation of study conduct, raw data, and analytical methods to support your regulatory filings.
Why Choose Us
Integrated In Vitro & In Vivo Platform: One team handles formulation, characterization, and preclinical testing, reducing hand-off delays and ensuring data consistency.
Flexible, Scalable Formulation: We can produce small-scale (microgram) screening batches through milligram quantities for rodent studies, with matched QC metrics.
Deep Preclinical Experience: Our scientists have extensive experience designing and executing nonclinical programs for mRNA-based therapeutics, including immunogenicity and safety assessments.
Regulatory-Aware Study Design: We consult on study designs that align with regulatory expectations for IND-enabling packages, helping you anticipate agency questions.
Backed by Creative Biogene: All projects are delivered under Creative Biogene's ISO-aligned quality system, with dedicated project management, milestone-based reporting, and full intellectual property protection for your data.
Target Cell Types Commonly Addressed
Our delivery systems can be tailored for mRNA delivery to a variety of immune cell populations. Examples include:
T Cells (CD4+ and CD8+): For in vivo CAR-T or TCR-T reprogramming, we optimize carrier surface properties to enhance T-cell targeting and reduce hepatocyte uptake.
Natural Killer (NK) Cells: NK cell delivery benefits from carriers designed to avoid opsonization and promote uptake through NK cell receptors (e.g., CD16, NKG2D).
Dendritic Cells (DCs): RNA delivery to DCs for vaccine applications is supported by LNPs that promote endosomal escape and cross-presentation.
Macrophages: We can adjust particle size and surface charge to preferentially target tissue-resident macrophages or circulating monocytes.
Contact Us
Whether you are screening carriers, refining lead candidates, or building a regulatory package, the scientific team at Creative Biogene can help you design the right experimental strategy—from formulation and assay selection to data interpretation. Reach out to discuss a tailored solution for your next project.
