Protein Replacement Therapy (PRT) treats diseases from missing/dysfunctional proteins, with mRNA-based PRT offering a superior approach—delivering genetic instructions for endogenous, transient therapeutic protein production via advanced modification and targeted LNP delivery. Creative Biolabs provides end-to-end solutions covering molecular design, scalable manufacturing, and targeted delivery, de-risking development stages, ensuring stable expression and precise targeting, and focusing on regulatory-compliant CQAs to accelerate clinical translation.
PRT is a therapeutic strategy aimed at replacing or supplementing a specific protein that is deficient or non-functional due to a genetic mutation or disease. The goal is to restore normal biological function. While highly effective, traditional PRT is limited by high manufacturing costs, protein stability challenges, and the need for frequent, high-dose administration.
Fig.1 Key quality attributes in the production of encapsulated mRNA products for white matter replacement therapy.1,3
The shift to mRNA delivery offers fundamental benefits that address the shortcomings of traditional protein infusions:
Creative Biolabs' customized service is designed to support diverse therapeutic applications:
A pilot project typically takes 8–14 weeks, depending on target protein complexity (e.g., multi-domain proteins need more optimization), delivery system novelty (e.g., new LNP ligands need validation), and in vivo model testing scope.
Perform in silico analysis, optimize codons for mammalian expression, select suitable UTRs, and strategically incorporate modified nucleosides (e.g., Pseudouridine, 5-Methylcytidine) to enhance translation efficiency and minimize innate immune activation.
Conduct high-yield in vitro transcription (IVT) of optimized plasmid templates in controlled bioreactors. Purify via Monolith Chromatography and Tangential Flow Filtration (TFF) to efficiently remove impurities (e.g., truncated products, dsRNA) for low immunogenicity.
Encapsulate purified mRNA into custom Lipid Nanoparticles (LNPs) using Microfluidic Technology. Precisely control self-assembly to tightly regulate Particle Size Distribution (PDI) and maximize Encapsulation Efficiency (EE).
Rigorously test formulations in relevant cell lines. Quantify transfection efficiency, measure therapeutic protein expression (e.g., ELISA, Western Blot), and perform initial immunogenicity screening (e.g., cytokine induction) to select lead LNP candidates.
Conduct comprehensive stability testing (thermal, shelf-life) on lead formulations. Perform in vivo studies to determine Pharmacokinetics, Pharmacodynamics, and initial Toxicity Profile, generating critical data for IND-enabling studies.
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The Creative Biolabs Protein Replacement Therapy related mRNA Development Service is a modular, customizable platform designed to meet your specific therapeutic and regulatory needs. We emphasize flexible service models, allowing clients to engage for a full end-to-end program or targeted optimization of a single component, such as LNP formulation or mRNA purification.
End-to-End, Integrated Development Pipeline
One-stop service spanning molecular design, IVT synthesis, LNP formulation, and comprehensive preclinical characterization for accelerated development.
Customized Molecular Engineering for Maximum Yield
Proprietary algorithms for gene/UTR optimization and strategic incorporation of modified nucleosides (e.g., Pseudouridine, 5-Methylcytidine) to achieve industry-leading protein expression and minimized innate immune response.
Precision LNP Formulation via Microfluidics
Utilization of advanced microfluidic technology to guarantee highly monodisperse nanoparticles (low PDI) and maximized Encapsulation Efficiency (EE), critical for reproducible biodistribution and high quality.
Scalable, High-Purity mRNA Manufacturing
Implementation of highly efficient upstream IVT and robust downstream purification methods, including Monolith Chromatography and TFF, to ensure superior removal of immunogenic double-stranded RNA (dsRNA) impurities.
Comprehensive Quality-by-Design Documentation
Well-established quality systems to generate full Certificates of Analysis and detailed Formulation Reports, ensuring seamless transition to GMP production readiness.
Flexible Delivery System Customization
Ability to customize lipid ratios, N:P ratios, and select from diverse delivery platforms (LNPs, Lipoplexes, Cationic Nanoemulsions) to optimize in vivo targeting for specific cell and tissue types.
In-Depth Preclinical PK/PD Profiling
Conducting comprehensive in vitro and in vivo assays to evaluate transfection efficiency, protein expression kinetics, initial toxicity, and pharmacodynamics data tailored to your target disease model.
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To enhance the transfection efficiency of mRNA in mRNA-related protein replacement therapies, the formulation of lipid nanoparticles used for delivering mRNA was optimized. The efficiency of different LNP preparations in transfecting mRNA into eukaryotic cells was evaluated. The HepG2 cell line demonstrates the highly efficient transfection ability of LNP.
Fig.2 mRNA was delivered using LNP of different formulations to detect its transfection efficiency.2,3
LNP-mRNA formulations are highly sensitive to physicochemical stresses. We address this through a comprehensive stability profiling program, including thermal stress testing and accelerated shelf-life studies. Our advanced LNP formulation process, achieved using microfluidics, often yields formulations that are stable for extended periods under refrigerated conditions, and we also provide guidance on lyophilization protocols where long-term deep-cold storage is a constraint.
Traditional bulk mixing often results in high polydispersity (PDI), meaning a mix of particle sizes and inconsistent encapsulation. Microfluidic technology provides precise, continuous, and rapid control over the mixing ratio and fluid dynamics at the nanoscale. This results in highly uniform, monodisperse LNPs (low PDI) with predictable biodistribution and maximized Encapsulation Efficiency, which is crucial for regulatory quality standards and reproducible clinical outcomes.
Immunogenicity is primarily managed by two factors. First, we use nucleoside modifications (like Pseudouridine) to prevent recognition by cellular sensors. Second, and critically, we use high-resolution purification techniques (Monolith Chromatography/TFF) to efficiently remove dsRNA and other reaction impurities. The key metric we track is the level of residual dsRNA (often kept below a strict threshold), which directly correlates with reduced cytokine induction in in vitro screening assays.
Our platform is highly versatile and capable of expressing virtually any protein blueprint, including complex enzymes (e.g., for Lysosomal Storage Disorders), secreted proteins (e.g., hormones, growth factors like VEGF-A), and structural proteins. We specialize in optimizing the mRNA sequence for robust and transient expression, regardless of the protein's size or function.
Our service drastically accelerates the timeline by eliminating several months of work associated with clone selection, cell line development, fermentation optimization, and complex, multi-stage protein purification required for traditional methods. With mRNA, once the sequence is optimized, IVT synthesis and LNP formulation can be achieved within weeks, significantly fast-tracking your lead candidate toward preclinical testing.
Creative Biolabs is the industry's trusted provider for the most advanced Protein Replacement Therapy related mRNA Development Service. We offer deep expertise in custom mRNA design, scalable IVT synthesis, and proprietary LNP formulation using gold-standard microfluidic technology. Our integrated, end-to-end platform is built on two decades of experience and a strict Quality by Design framework, ensuring your therapeutic pipeline is efficient, compliant, and poised for clinical success.
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| Cat. No | Product Name | Promoter |
|---|---|---|
| GTVCR-WQ19MR | IVTScrip™ pT7-VEE-mRNA-Anti-H1-0, (131)I-chTNT-1/B Vector | T7 |
| GTVCR-WQ22MR | IVTScrip™ pSP6-VEE-mRNA-Anti-H1-0, (131)I-chTNT-1/B Vector | SP6 |
| GTVCR-WQ24MR | IVTScrip™ pT7-VEE-mRNA-Anti-KDR, 1121B Vector | T7 |
| GTVCR-WQ25MR | IVTScrip™ pSP6-VEE-mRNA-Anti-KDR, 1121B Vector | SP6 |
| GTVCR-WQ28MR | IVTScrip™ pT7-VEE-mRNA-Anti-EGFR, 11F8 Vector | T7 |
| Cat. No | Product Name | Type |
|---|---|---|
| GTTS-WQ15MR | IVTScrip™ mRNA-Anti-S, 2130(Cap 0, 5-Methyl-CTP & Pseudo-UTP, 120 nt-poly(A)) | Antibody |
| GTTS-WQ16MR | IVTScrip™ mRNA-Anti-S, 2130(Cap 1, 5-Methyl-CTP & Pseudo-UTP, 120 nt-poly(A)) | Antibody |
| GTTS-WQ17MR | IVTScrip™ mRNA-Anti-S, 2130(Cap 0, 5-Methyl-CTP & Pseudo-UTP, 30 nt-poly(A)) | Antibody |
| GTTS-WQ18MR | IVTScrip™ mRNA-Anti-S, 2130(Cap 1, 5-Methyl-CTP & Pseudo-UTP, 30 nt-poly(A)) | Antibody |
| GTTS-WQ19MR | IVTScrip™ mRNA-Anti-S, 2130(Cap 0, Pseudo-UTP, 120 nt-poly(A)) | Antibody |
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