The service offers cutting-edge non-viral gene delivery via VEEVLPs—structurally precise, non-infectious Alphavirus-derived nanoparticles that package self-amplifying RNA (saRNA). They solve traditional nucleic acid therapeutics' stability/expression issues and act as a potent vaccine platform, inducing strong protection.
It helps overcome delivery bottlenecks via replicase-mediated amplification and high-efficiency delivery, builds in vivo bioreactors for high-level transient expression, and leverages decades of Alphavirus expertise to deliver validated, low-dose candidates for preclinical testing.
VEEVLP is an envelope for efficient cytoplasmic delivery. After host cell internalization, its saRNA payload is released and uses nsp1-4 proteins to form the RdRp complex. This complex amplifies saRNA into massive copies (and subgenomic RNA with therapeutic genes), driving high-level, sustained target protein expression—turning host cells into temporary micro-factories. The process stays in the cytoplasm, with no genomic integration risk.
Our process is meticulously structured to ensure a clear, traceable, and quality-controlled development cycle, minimizing risk and maximizing efficiency for your project.
To initiate the service, clients provide:
Codon-optimize the target gene and seamlessly clone it into the VEEV Replicon Plasmid, replacing the native structural genes. This ensures the Self-Amplifying mRNA (saRNA) contains the viral replicase machinery (nsp1-4) while remaining replication-defective for viral spread.
Engineer complementary Helper Plasmids to separately express the VEEV structural proteins (E1 and E2 glycoproteins) needed to form the VLP shell. This strict separation prevents the generation of spreading, infectious viruses.
Co-transfect or infect the chosen high-yield expression system with the Replicon Plasmid (containing the saRNA payload) and Helper Plasmids. The structural proteins then assemble around the saRNA to package it into a VEEVLP, producing a crude high-titer VEEVLP product.
Purify VEEVLPs from the culture supernatant using advanced techniques like Tangential Flow Filtration (TFF) and specialized chromatography. Conduct a comprehensive QC battery afterward, assessing structural integrity (via Electron Microscopy), purity, and titer (measured as infectious units/mL) to generate a certified, clinical-grade VEEVLP lot.
Test the final VEEVLP product on target cells in vitro. Quantify the expression levels of the therapeutic protein (e.g., via Western Blot or ELISA) to confirm the amplification effect and functional payload delivery.
Estimated Timeframe: The typical timeframe for this service ranges from 8 to 14 weeks, depending on the complexity of the insert gene, the required production scale, and the stringency of the final QC package.
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Creative Biolabs provides robust, end-to-end VEEVLP manufacturing services designed to transition your concept from the bench to preclinical testing with speed and uncompromising quality. We offer fully customizable solutions for every stage of your product's lifecycle.
Full-spectrum service from laboratory-scale proof-of-concept and pilot batches up to large-scale industrial manufacturing. We deploy high-volume stirred-tank bioreactors, offering over 100,000 liters of total capacity, ensuring your long-term supply security.
Highly efficient upstream (VLP expression yield maximization) and downstream purification development. We customize the packaging process—running in batch, fed-batch, or continuous (perfusion) mode—to maximize VLP titer and optimize culture conditions specifically for your therapeutic cargo.
Your project is governed by a Well-established Quality System. Our production pathways are GMP-certified, implementing QbD principles, validated Process Analytical Techniques (PAT), and the HACCP approach to guarantee stringent aseptic verification and consistent, verifiable quality throughout the entire process.
Dedicated services to optimize the codon usage of your target gene for maximal expression via the VEEV replicase. We perform strict QA assessment and guarantee the stability of all critical components, including Helper Plasmid systems and Master Cell Banks (MCB), crucial for regulatory success.
High-standard quality control tools are used to quantify and evaluate the final VLP lot. This includes functional potency assays that directly measure the amplification factor and biological activity, ensuring the therapeutic payload is precisely characterized and ready for preclinical release.
The AAHI-SC2 vaccine contains a saRNA replicator, which consists of an 11.7 kb construct for expressing the SARS-CoV-2 S protein, as well as the non-structural proteins 1-4 of the Venezuelan equine encephalitis virus (VEEV) vaccine strain.
Fig.1 Sequence design of saRNA(D614G)-2P-3Q-NLC (AAHI-SC2) vaccine.1
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The VEEVLP is engineered to be extremely safe. It is replication-deficient because the structural genes required for packaging are provided in trans on separate Helper Plasmids. The final VLP contains only the self-amplifying therapeutic RNA, ensuring it can only undergo a single round of expression in the patient's cells and cannot generate new, infectious viral particles.
While LNPs are effective, VEEVLPs offer the unique benefit of self-amplification. This means one VEEVLP delivers one saRNA that produces hundreds or thousands of copies of the therapeutic RNA, whereas one LNP delivers one conventional mRNA molecule. This translates directly to significantly higher protein yield and lower required dosing for VEEVLP-based candidates.
Our service provides extensive customization. The VEEV replicon allows for the insertion of various genetic payloads, including large antigens, fused proteins, and even antibody-encoding sequences. We perform tailored replicon construct optimization to accommodate gene size and ensure the highest expression efficiency for your specific therapeutic goal.
The VEEVLP's primary advantage is its ability to mimic a natural viral infection structurally, combined with the saRNA's internal signaling. This dual action elicits both a powerful humoral (antibody) response and a robust, often more crucial, cellular (T-cell) immune response, which is essential for durable protection and fighting intracellular pathogens.
Creative Biolabs is your dedicated partner in harnessing the transformative power of the Custom Venezuelan Equine Encephalitis Virus-Like Particle (VEEVLP) Development Service. By integrating the high-efficiency delivery of the VLP with the potency of self-amplifying RNA, we provide a pathway to therapeutic candidates characterized by high efficacy, low dose, and rapid development cycles.
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| Cat. No | Product Name | Promoter |
|---|---|---|
| GTVCR-WQ79MR | IVTScrip™ pT7-VEE-mRNA-Anti-AMHR2, 3C23K Vector | T7 |
| GTVCR-WQ82MR | IVTScrip™ pSP6-VEE-mRNA-Anti-AMHR2, 3C23K Vector | SP6 |
| GTVCR-WQ83MR | IVTScrip™ pT7-VEE-mRNA-Anti-PDGFRA, 3G3 Vector | T7 |
| GTVCR-WQ86MR | IVTScrip™ pSP6-VEE-mRNA-Anti-PDGFRA, 3G3 Vector | SP6 |
| GTVCR-WQ87MR | IVTScrip™ pT7-VEE-mRNA-Anti-SELP, 42-89-glycoprotein Vector | T7 |
| Cat. No | Product Name | Type |
|---|---|---|
| GTTS-WQ45MR | IVTScrip™ mRNA-Anti-TNFRSF17, 2857916(Cap 0, N1-Methylpseudo-UTP, 30 nt-poly(A)) | Antibody |
| GTTS-WQ46MR | IVTScrip™ mRNA-Anti-TNFRSF17, 2857916(Cap 1, N1-Methylpseudo-UTP, 30 nt-poly(A)) | Antibody |
| GTTS-WQ47MR | IVTScrip™ mRNA-Anti-TNFRSF17, 2857916(Cap 0, 5-Methoxy-UTP, 120 nt-poly(A)) | Antibody |
| GTTS-WQ48MR | IVTScrip™ mRNA-Anti-TNFRSF17, 2857916(Cap 1, 5-Methoxy-UTP, 120 nt-poly(A)) | Antibody |
| GTTS-WQ49MR | IVTScrip™ mRNA-Anti-TNFRSF17, 2857916(Cap 0, 5-Methoxy-UTP, 30 nt-poly(A)) | Antibody |
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