Discover uBriGene’s RNA-LNP manufacturing platform and proprietary microfluidic LNP formulation technology, designed to reduce costs and accelerate timelines for therapeutic developers.
The efficacy and safety of RNA-based therapeutics and vaccines rely on manufacturing high-quality RNA and encapsulating into optimal lipid nanoparticles (LNP). uBriGene provides an end-to-end CMC solution to developers of RNA-based medicines.
| Types of services | Description | Estimated Timeline | Pricing | |
|---|---|---|---|---|
| mRNA | mRNA Production | Custom mRNA production service for preclinical applications, mg to grams quantity | 2 weeks | Please Inquire |
| mRNA-LNP Production | mRNA production and LNP formulation service for preclinical applications | 2 Weeks | ||
| circRNA | circRNA production | Custom circRNA production service for preclinical applications, mg to grams quantity | 2 Weeks | |
| circRNA-LNP production | circRNA production and LNP formulation service for preclinical applications | 2 Weeks | ||
| saRNA | saRNA Production | Custom saRNA production service for preclinical applications, mg to grams quantity | 2 Weeks | |
| saRNA-LNP Production | saRNA production and LNP formulation service for preclinical applications | 2 Weeks | ||
| sgRNA-IVT | sgRNA Production | Custom sgRNA in vitro transcription service for preclinical applications, mg to grams quantity | 2 Weeks | |
| sgRNA-LNP Production | sgRNA production and LNP formulation service for preclinical applications | 2 Weeks | ||
| GMP Services | GMP RNA / RNA-LNP Manufacturing | GMP RNA, RNA-LNP process development, tech transfer, manufacturing and testing | Varies | |
| Types of services | Description | Estimated Timeline | Pricing | |
|---|---|---|---|---|
| mRNA | mRNA Production | Custome mRNA prodution services for preclinical application, mg to gram quantity | 2 weeks | Please Inquire |
| mRNA-LNP prodution | mRNA production and LNP formulation service for preclinical applications | 2 Weeks | ||
| circRAN | circRNA production | Custom circRAN prodution service for preclinical application, mg to gram quantity | 2 Weeks | |
| circRNA-LNP production | circRAN production and LPN formulation services for preclinical applications | 2 Weeks | ||
| saRNA | saRNA production | custom saRNA roduction service for preclinical application, ma to gram quantity | 2 Weeks | |
| saRNA-LNP production | saRNA production and LNP formulation service for preclinical application | 2 Weeks | ||
| sgRNA-IVT | sgRNA prodution | custome sgRNA in vitro transcrition service for preclinical application, mg to gram quantity | Weeks 2 | |
| sgRNA-LNP production | sgRNA production and LPN formulation service for preclinical application | 2 Weeks | ||
| GMP Serrvices | GMp RNA /RNA-LNP Manufacturing | GMP RNA, RNA-LPN process Development, tech-transfer,manufacturing and testing | Varies | |
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With our high productive RNA manufacturing platform and RNA-LNP formulation technologies, we can accelerate your RNA therapeutic and vaccine programs.
uBriGene has developed the capability to manufacture mRNA, circular RNA (circRNA), and self-amplifying RNA (saRNA) for gene modification and vaccine therapeutic programs. Below is the generic workflow for mRNA and saRNA-LNP production. circRNA needs an additional circularization step after in vitro transcription. The most used RNA circularization method is the PIE method, in vitro circularization using group I introns.
Our innovative in vitro transcription of single-guide RNA (sgRNA) is a much more scalable and cost-effective process than chemical synthesis. Details about sgRNA-IVT can be found at GMP sgRNA-IVT manufacturing services.
mRNA/saRNA manufacturing workflow diagram
uBriGene has developed a scalable, cost-effective and time-reducing RNA-LNP manufacturing process that is adaptable to various RNA modalities (mRNA, circRNA, saRNA, and sgRNA) and lipid chemistries.
Key steps of our microfluidic RNA-LNP encapsulation technology include high-speed mixing of lipids and RNA solution, tangential flow filtration (TFF) for buffer exchange and RNA-LNP concentration, followed by sterile filtration and final product fill/finish..
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Fig. 1. eGFP is highly Expressed in Cells with uBriGene Produced mRNA-LNP
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Fig. 2. RNA-LNP formulation screening studies. Eight different LNP formulations (horizontals) have been screened for high GFP expression in different cell lines. GFP mRNA was used for this LNP formulation study. A: Glial cell line, B: Neuronal cell line, C: Macrophage cell line, D: Spermatocyte cell line.
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Fig. 3. RNA-LNP formulation screening studies in eight different culture media. GFP mRNA-LNP was used for this study. Horizontals are eight different cell culture media. A: Glial cell line, B: Neuronal cell line, C: Macrophage cell line, D: Spermatocyte cell line.
| mRNA | Circular RNA | |
|---|---|---|
| Format | Linear | Circular |
| 5’ Capping, PolyA tailing? | Yes | No |
| Expression mechanism | 5' cap structure + Kozak translation initiation site | IRES |
| Intracellular stability | Lower (within a week), dependent on capping efficiency and the length of polyA tail | Higher (around two weeks), no need for 5’ cap and polyA structure |
| Coding sequence limitations | Long, dependent on the upper limit of in vitro transcription enzymes | Circularization efficiency decreases as the length increases |
| Production yield | High in vitro transcription yield | High in vitro transcription yield, need additional steps to remove linear RNA |
| Expression intensity | High transient expression intensity, followed by rapid decline | Comparable to mRNA expression with better persistence |
| Immunogenicity | High | Low |
| Applications | Applications requiring rapid expression of proteins | Applications requiring prolonged protein expression |
Viral vectors show high target cell delivery, but have multiple drawbacks compared to non-viral delivery systems such as RNA-LNP formulations. This includes inducing immune responses, which limits viral vector utility for repeat dosing. Other advantages of RNA-LNP vs viral vectors include: a lower risk of genome integration; co-formulation of multiple RNA in a single LNP (very valuable for gene editing applications utilizing Cas mRNA and sgRNA); LNPs can carry larger payloads than viral vectors.
We can provide commercially available lipids. We can work with your custom lipids as well, helping perform process development and tech transfer for your RNA-LNP formulation.
The composition and ratios of the lipids incorporated into an LNP-based therapeutic/vaccine dramatically impact the quality, biodistribution, and stability of the LNP. Clinically impactful RNA-LNPs have typically used a combination of ionizable lipids, PEGylated lipids, phospholipids, and cholesterol.
Reproducible RNA-LNP formulation requires careful control of the following Critical Process Parameters (CPP): lipid combinations and ratios, chemical conditions and flow rate during mixing; TFF and sterile filtration consumables and conditions that minimize RNA-LNP shearing; fill/finish conditions (preferably automated); and an optimal closure/vial combination that ensures RNA-LNP stability.
Analytics are required for: particle size distribution (DLS); payload quantification & encapsulation efficiency [LC-MS (lipids) & LC-UV & fluorescence (RNA)]; surface charge/zeta potential (ELS); impurity measurements (template DNA, gDNA, lipids, dsRNA via CE & LC-MS/UV/LIF); safety (bioburden, endotoxin).
mRNA is generated by a multi-enzyme in vitro transcription (IVT) process. IVT efficiency is impacted by many variables, including DNA template quality/purity; DNA template design – promoter, 5’ & 3’ UTRs, polyA tail length; DNA template ORF sequence – hairpins & repetitive sequences lower IVT efficiency; desired length of RNA transcript; use of modified rNTPs during IVT; RNA polymerase; capping strategy; reaction buffer and final product storage buffer; RNase levels.
Separating circular RNA from its linear form is a significant challenge in circRNA purification. uBriGene has dedicated extensive efforts to downstream purification and can achieve up to 94% purity.
We manufacture circRNA using the PIE method. Our breakthrough in purification, which effectively removes linear RNA, enables us to achieve over 90% circRNA purity.
Manufacturing intact full-length saRNA is challenging due to its size. uBriGene’s process development team has optimized saRNA production and purification, achieving up to 80%-90% integrity, depending on the sequence.
sgRNA produced with uBriGene’s innovative in vitro transcription method has been tested to show higher gene editing efficiency than chemically synthesized guide RNA.
saRNA refers to self-amplifying RNA, which is a type of RNA molecule derived from alphavirus that can replicate itself within a host cell, which is a concept used in certain vaccine technologies.
Circularization is an intramolecular reaction highly sensitive to conditions such as substrate concentration, temperature, and ion strength. Enhancing circularization efficiency and completely removing linear RNA from the circularized product are key challenges in circRNA manufacturing.
Tap into our mRNA, circRNA, and saRNA manufacturing and LNP formulation expertise, focus your time on discovery research!
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