The Perfect Fit for Nucleic Acid Therapeutics

Plasmid DNA Engineering 

Plasmid DNA engineering for therapeutics involves the design and modification of plasmids to deliver therapeutic genes into cells. These plasmids can carry DNA encoding proteins that correct genetic defects, stimulate immune responses, or treat diseases. Engineering plasmids includes optimizing gene sequences and incorporating regulatory elements to improve efficacy, safety and cost-effectiveness of the nucleic-acid based therapeutic treatment. 

Challenge: Plasmid DNA as a template needs to be carefully engineered to ensure efficient mRNA synthesis, scalability and safety.

Solution: Custom design your own plasmid and rely on plasmid experts to optimize each element of your plasmid DNA template.

Highlight products supporting plasmid DNA engineering 

• Plasmid Engineering Service offers custom plasmid engineering based on a unique DNA brick approach to enable fast and precise engineering of any plasmids, even the most complex ones with a success rate above 95%

Design My Plasmid

Plasmid DNA Production 

Plasmid DNA is produced in host cell bacteria, typically E. coli. and then harvested once the desired yield and density are reached.

Challenge: Optimizing plasmid yield, maintaining plasmid stability, and ensuring consistent quality are paramount. Plasmid DNA as a template for mRNA production needs to meet purity and quality requirements to ensure consistent, scalable, and high-yield production.

Solution: Rely on robust manufacturing and analytics platforms to ensure highest percentage of supercoiled DNA and highest purity by minimizing presence of contaminants such as endotoxins. 

Highlight products supporting plasmid DNA production 

• Plasmid Manufacturing Service excels in producing pDNA at high-quality with superior yields and supercoiled integrity.  Each plasmid DNA produced is provided with regulatory support to ensure compliance for clinical trials and commercial use

• Cornerstone Development Service is designed to support customers in establishing in-house pDNA production processes at the required scale and that is then seamlessly transferred to each customer site

   

Plasmid DNA Purification  

Plasmid DNA purification for therapeutics often requires complex, multi-step processes like alkaline lysis, centrifugation, and chromatography, which can be time-consuming and costly. Ensuring high-quality, endotoxin-free plasmid DNA is crucial for therapeutic applications.

Challenge: Purification faces several bottlenecks including challenges in scalability, decreasing unwanted impurities such as host cell genomic DNA and RNA, and achieving high yield recovery.

Solution: Adopt innovative purification solutions that maximize both yield and quality of plasmid DNA, or outsource your plasmid manufacturing to our nucleic acid experts to reduce your therapeutic development time.

Highlight products supporting plasmid DNA purification  

• Plasmid Manufacturing Service to outsource end-to-end plasmid DNA production to achieve highest quality, purity, and batch-to-batch reproducibility. Plasmids can be linearized. All plasmids produced are free of endotoxins, host germline DNA and mRNA, and host-cell proteins (HCPs)
• Cornerstone Development Service is designed to support customers in establishing in-house pDNA purification processes at the required scale and that is then seamlessly transferred to each customer site
• HiP²  Plasmid Process Pack is a set of ready-to-use monolithic columns (CIM^® DEAE and CIM^® C4 HLD) for pDNA purification intended to help scientists develop their own pDNA purification process and transfer it to production
• PATfix^® pDNA Analytical Platform enables in-process control of pDNA isoform and multimer separation to accelerate process development and ensure product quality
• Alkalizator  is a fully automated in-line lysis system designed to increase control and efficiency of pDNA isolation from bacterial cells, while decreasing unwanted impurities such as host cell genomic DNA and RNA.

mRNA Synthesis 

mRNA production involves several critical steps, with in vitro transcription (IVT) playing a key role. IVT is an RNA polymerase-driven reaction that synthesizes messenger RNA (mRNA) from a DNA template. 

Challenge: Monitoring mRNA synthesis and achieving high mRNA yield are critical to ensure cost-effectiveness. 

Solution: Improve mRNA synthesis monitoring in real time and enhance purification methods for high purity mRNA production.    

Highlight products supporting mRNA synthesis 

• PATfix^® mRNA Analytical Platform is designed to perform at-line instantaneous monitoring to quantify mRNA recovery, IVT components and by-product impurities
• CIMac Analytical Columns are high-performance chromatography tools designed for rapid, high-resolution and flow-independent separations instantaneously

mRNA Purification  

Following mRNA synthesis, chromatography methods are used to remove impurities and recover the mRNA.

Challenge: Minimize the presence of impurities, such as residual DNA, and unincorporated nucleotides while ensuring scalability of the process.

Solution: Enhance capacity, binding and recovery of mRNA using specifically designed columns, while ensuring close monitoring of the process.

Highlight products supporting mRNA purification  

• CIMmultus^® Oligo dT is a high-performance column primarily intended for capturing ssRNA with a poly-adenylated tail, making it an excellent tool for the purification of mRNA in IVT reaction mixtures
• CIMmultus^® Swiper offers versatile RNA purification, high recovery rates, and cost efficiency for various RNA types,, with stable, scalable processing.
• PATfix^® mRNA Platform  is designed to perform at-line instantaneous monitoring to quantify mRNA recovery, IVT components and by-product impurities
• Cornerstone Development Service is designed to support customers in establishing in-house mRNA purification processes at the required scale and that is then seamlessly transferred to each customer site

mRNA Formulation

The purified mRNA is encapsulated into the non-viral delivery vehicle, which could be liposomes, polymeric nanoparticles, or lipid nanoparticles for example. These vessels protect the mRNA during delivery.

Challenge: Achieving optimal encapsulation efficiency, ensuring stability and improving targeted delivery to extra-hepatic tissues.

Solution: Rely on innovative delivery solutions that ensure stability and effective delivery. 

Highlight products supporting mRNA formulation

• LipidBrick^® is a library of innovative cationic lipids to optimize LNP formulation and enable extrahepatic biodistribution
• in vivo-jetRNA^®+ is ready-to-use and offers an alternative to LNP formulation to enable targeted delivery to unique or multiple organs using local or systemic injection routes
• PATfix^® - LNP Switcher Platform is a chromatography-based analytical platform tailored for lipid nanoparticle (LNP) characterization, enabling real-time separation, quantification, and process control to accelerate nucleic acid–based therapeutic development.