Development and commercialization of therapeutics involving new and emerging technologies present the market with new challenges, from establishing secure supply chains of critical raw materials to creation of customized solutions. At Thermo Fisher Scientific, we rise to this challenge by applying our breadth and depth of technologies and resources to support your efforts. Let us help select the right products for your applications.
Our solution to address all aspects of mRNA therapeutic development
- Comprehensive selection of Thermo Scientific TheraPure in vitro transcription reagents
- Verified Invitrogen Dynabeads magnetic beads for superior analytical reproducibility
- Extensive library of proprietary delivery reagents
- Custom gene synthesis with GeneArt GeneOptimizer to maximize expression of your synthetic genes
- Innovative POROS Oligo (dT)25 affinity resin for selectivity and capacity requirements
- Scalable systems support early-stage research through clinical development and commercialization
- Leading innovation driven by continual process optimization
- Dedicated team of technical experts
- Superior quality management system
- Flexible licensing options
- TheraPure enzymes (animal origin-free and ampicillin-free)
- NTPs and modified nucleotides
- Invivofectamine Rx Reagent
Accelerated development of mRNA-based therapeutics has necessitated the transformation of standard, research-grade in vitro transcription (IVT) reagents into raw materials specifically designed and manufactured under advanced quality standards (Table 1). TheraPure reagents for mRNA therapeutics provide our partners access to the most experienced development, analytical, and manufacturing teams in the industry.
Table 1. In vitro RNA synthesis solution.
Animal origin-free (AOF) and ampicillin-free (AF) enzymes
The TheraPure enzymes for in vitro transcription are manufactured under stringent animal-free and ampicillin-free processes. These enzymes are grown in media and purified completely without animal-sourced components. Our AOF manufacturing process eliminates potential prion (bovine spongiform encephalopathy and transmissible spongiform encephalopathy) and virus-derived disease risks. Components of animal origin are replaced with AOF components throughout the manufacturing process—from fermentation to enzyme formulation.
The absence of animal-derived materials in the manufacturing process minimizes the need for excessive traceability documentation and accountability. In addition, the AOF enzymes help to reduce the risk of ampicillin-related allergic reactions and other side effects.
Generation of mRNA by in vitro transcription includes several cleanup steps. Traditional purification techniques, like phenol:chloroform followed by precipitation or spin-column, have limited capacity with multiple steps and are not easily automated. On the other hand, magnetic bead-based technologies are flexible, scalable, and automation friendly. An mRNA purification protocol based on Invitrogen Dynabeads MyOne Carboxylic acid and a proprietary binding buffer can deliver higher yield than traditional purification methods.
Purification by generic capture
- Invitrogen Dynabeads MyOne Carboxylic Acid for generic capture of mRNA (Figure 1)
- In-process purification
- Optimized buffers available under confidential disclosure agreement
- Increased mRNA concentration
Figure 1. Capture workflow with Invitrogen Dynabeads MyOne Carboxylic Acid.
- Up to 1.6 mg mRNA per mg Dynabeads MyOne Carboxylic Acid
- Flexible and scalable protocol with a high recovery rate (Figure 2)
Figure 2. High mRNA recovery rate as determined using the Invitrogen Qubit 4 Fluorometer.
As a world leader in providing in vitro transfection reagents, our committed team of scientists continually develops evolving technologies to meet the growing demands for the latest mRNA delivery formulations, especially for therapeutic applications. Our in vivo mRNA delivery platform provides optimal organ delivery with minimal toxicity in small animal models (Table 2).
Table 2. In vivo mRNA delivery solution.
|Technology||Invivofectamine Rx mRNA|
|Potency||In vivo luminescence (1 x 1010 photons/sec) at 1 mg/kg mRNA dose|
|Specificity*||Liver, spleen, lung, intramuscular—other tissues may be accessible*|
* Please inquire via email
Optimized proprietary delivery
We utilize a combinatorial method to identify novel compounds and optimize formulations specific for different RNA payloads through proven design of experiment (DoE) and extensive proprietary know-how in the field of transfection (Figure 3).
- Extensive screening of potential candidates to select the optimal LNP formulations
- DoE for optimizing LNP formulation process parameters
Figure 3. Schematic of design of experiment (DoE) and formulation screening.
High-efficiency mRNA delivery
Invitrogen Invivofectamine Rx Reagent provides a method for in vivo mRNA delivery (Figure 4), allowing our partners to accelerate their research and development of new technologies.
- Multicomponent, proprietary lipid nanoparticles
- Uniformly sized (90 nm) >90% encapsulation efficiency
- Potency demonstrated by in vivo luminescence (1 x 1010 photons/sec) at 1 mg/kg mRNA dose (Figure 4)
- Specificity shown in liver, spleen, lung, and muscle
- Scalable process
Figure 4. Sequential improvement in performance of reagents through DoE. in vivo delivery of luciferase mRNA (FLuc) using Invitrogen Rx mRNA demonstrating continuous improvement in reagent delivery performance as shown in (A) visual and (B) quantitative assessment of luciferase expression 4 hours post-IV injection in mice.
Assistance with ordering, order status, and invoices
Technical assistance for all TheraPure product inquiries and selections, troubleshooting, and technical questions
Business development manager
Help navigate regulatory processes, custom products, and service offering from research to commercialization