Plasmid-to-LNP Continuum │ Digital QC │ GMP Lot Release
Messenger RNA has reshaped the speed and scope of modern therapeutics—from rapid-response vaccines to in-vivo gene-editing payloads. Elise Biopharma delivers an integrated, end-to-end mRNA platform that unites plasmid DNA manufacture, high-yield IVT, cutting-edge LNP encapsulation, and robotic aseptic fill-finish—all under one quality system. Whether you’re advancing an infectious-disease vaccine, an oncology cytokine, or a self-amplifying RNA therapeutic, we provide the velocity, fidelity, and regulatory depth to carry your molecule from research bench to commercial launch.
Plasmid DNA Foundation
A potent mRNA starts with a clean, supercoiled template.
Microbial Fermentation & Purification
- CRISPR-edited E. coli strains with RNAse-deficient background and antibiotic-free selection reduce endotoxin and antibiotic-residue concerns.
- Fed-batch processes reach 2–4 g L⁻¹ plasmid in 200-L and 2 000-L fermentors; scalable alkaline-lysis and multi-step chromatographic polishing deliver ≥95 % supercoiled purity.
Quality & Regulatory Readiness
- Residual genomic DNA < 1 % (qPCR) and endotoxin < 0.1 EU mg⁻¹.
- Full suite of release assays—restriction mapping, sequencing, supercoil ratio, residual host-cell protein—compiled into DMF-ready documentation.
High-Yield In-Vitro Transcription
Optimised IVT chemistry drives RNA output while preserving integrity.
- Enzymatic Kits at Scale — proprietary high-processivity T7 polymerase and CleanCap®/TriLink-compatible cap analogues.
- Transcription Reactors — jacketed single-use vessels (0.5–50 L) with inline temperature, pH, and magnesium sensors; real-time HPLC sampling tracks NTP consumption and abortive species.
- Elevated Yields — up to 10 g finished mRNA per 50 L reaction, RIN > 8.0, dsRNA < 0.1 %.
- Self-Amplifying RNA (saRNA) workflows supported, including replicon plasmid generation and DMOE-free IVT protocols.
mRNA Purification & QC
Downstream robustness ensures clinic-grade purity.
- Enzymatic DNAse digestion, tangential-flow UF/DF (100-kDa), and core-shell HPLC polishing bring residual template DNA < 10 pg µg⁻¹ and protein < 50 pg µg⁻¹.
- Chromatographic dsRNA depletion verified by anti-dsRNA ELISA and dot-blot.
- Intact-mass LC-MS and capillary electrophoresis confirm final length and cap/poly-A integrity.
Lipid Nanoparticle Formulation
Encapsulation determines transfection—and fate.
- Microfluidic Mixing—NxGen staggered-herringbone chips yield 60–100 nm particles with PDI ≤ 0.05 and encapsulation efficiency ≥ 95 %.
- Versatile Lipid Library—approved ionisable lipids (MC3, SM-102, ALC-0315) plus custom syntheses for tissue targeting.
- Real-Time PAT—dynamic light scattering in a closed loop feeds back to flow-rate ratios and total lipid concentration, locking size within ±3 nm batch-to-batch.
- Sterile Final Filter—0.22 µm PES filtration in ISO 5 isolators; aseptic connection to fill line avoids freeze/thaw damage.
Fill-Finish & Stability Science
- Robotic Isolator Lines fill vials or pre-filled syringes between –20 °C and +8 °C, employing nitrogen overlay to protect oxidation-sensitive lipids.
- Lyophilised LNP Option using sucrose-trehalose matrix delivers room-temperature stability for >6 months (accelerated 40 °C/75 % RH = 30 days).
- ICH-Compliant Stability — real-time, accelerated, and freeze/thaw cycles with periodic size, encapsulation, potency, and sterility checks.
Digital-First Quality & Compliance
All manufacturing data—IVT batch PDFs, PAT feeds, environmental monitoring—flows into a 21 CFR Part 11 electronic batch record. Our facility is cGMP & ISO 13485 certified, FDA-registered for IVD reagents, and supported by RA/QA scientists who have led IND and EUA filings for mRNA vaccines and cytokine therapeutics alike.
Engagement Tracks
| Model | Scope | Timeline |
|---|---|---|
| Template-to-Tox | Plasmid → 50 g non-GMP mRNA/LNP | ~4 months |
| Gene-to-IND | Plasmid, IVT, LNP, GMP DS + CMC dossier | 9–12 months |
| Commercial Ramp-Up | PPQ, CPV, annual capacity >100 M doses | Program-dependent |
Why Elise for mRNA?
- Single-Site Continuity — plasmid, IVT, LNP, and fill-finish under one QMS.
- Digital Precision — PAT + digital twins cut optimisation cycles by 30 %.
- Scalable Speed — 50 µg research lots to multi-kilogram GMP in the same reactors.
- Dual Compliance — therapeutic (cGMP) and diagnostic (ISO 13485) in parallel.
- Future-Proof Flexibility — saRNA, circular RNA, and split-lipid formulations already in process library.
Accelerate Your mRNA Modality
Partner with Elise Biopharma to move your mRNA—or saRNA—program from plasmid DNA to patient-ready vial on timelines that meet global health demands.