Nucleic Acid Therapeutic Development Solutions

Scale of production for RNA embedded within lipid nanoparticle

Nucleic acid therapeutics hold great promise for treating a wide range of diseases—we invite you to partner with us to reach your nucleic acid therapeutics development goals. Explore our portfolio of high-quality raw materials designed for your oligonucleotide and mRNA synthesis to help you move your project from development to manufacturing and commercialization. Thermo Fisher Scientific provides expertise, services, and support to help you accelerate your productivity and innovation.

Platforms enabling nucleic acid therapeutic manufacturing across the globe

Our manufacturing facilities and platforms, located in geographic raw material centers of excellence, are deeply rooted in enzymology, nucleic acid chemistry, bioprocessing, and lipid chemistry.

Products and services from centers of excellence for NA therapy workflow

Gene synthesis Regensburg, Germany	IVT RNA synthesis Vilnius, Lithuania	IVT RNA synthesis Milwaukee, WI, USA	Transcript purification Oslo, Norway and Bedford, MA, USA	Formulation and delivery Carlsbad, CA, USA
ISO 9001 certified Neoantigen sequencing Gene synthesis services Vector prep	ISO 9001, 13485 certified In vitro transcription enzymes Accessory enzymes Nucleotides Master mixes	ISO 9001 certified Phosphoramidites Modified nucleotides Chemulation Custom chemistry development and manufacturing Delivery molecules	ISO 9001, 13485 certified Invitrogen Dynabeads MyOne Carboxylic Acid Isolation/activation beads and magnets Custom bead development Thermo Scientific POROS oligo (dT) purification	ISO 9001 certified Proprietary lipid library Optimized Invitrogen Invivofectamine 3.0 Reagent formulation for in vivo delivery Scalable platform

TheraPure quality for mRNA and oligonucleotides synthesis

TheraPure reagents from Thermo Fisher Scientific are designed for pharmaceutical manufacturers looking for core building blocks to use in research and manufacturing. These reagents are crafted in facilities with thoroughly documented quality systems and audited by accredited drug products manufacturing authorization holders. Strategically designed and carefully manufactured following the principles of 21 CFR 210/211, The Rules Governing Medicinal Products in the European Union, volume 4 GMP Part II and ICH Q7, TheraPure reagents help build the solutions to today’s challenges.

The reagent attributes that differentiate TheraPure from catalog products include:

Table 1. Comparison of TheraPure reagents to catalog products by application.

		TheraPure reagents		Catalog reagents
		GMP grade	Research and clinical development grade	Research use only (RUO)
Quality	QMS	Principle of 21 CFR 210/211 and ICH Q7 ISO 9001:2016 ISO 13485:2016	ISO 9001:2016 ISO 13485:2016	ISO 9001:2016
		Quality Agreements with advanced therapy medicinal products MAH and notification system	Change control subject to contractual	No change control
		Validated for each product	Validated for product families	Validated for product families or not validated
Technology	Host & Scale	Novel proprietary hosts that bring industrial scale enzyme batch yields and total capacity outputs	Conventional Research Use Only (RUO) grade hosts for small to medium scale	Conventional Research Use Only (RUO) grade hosts for small to medium scale
	Strain/Plasmid	Qualified and characterized MCB/WCB Optimized high level extracellular expression	Low efficiency expression system, intracellular expression	Low efficiency expression system, intracellular expression
	Process	Inter-connected flow processes, vertically integrated layout Quality control	Open and non-inter-connected processes	Open and non-inter-connected processes
	Materials	Pharma grade, AOF, full traceability	Molecular biology grade (AOF for AOF products only)	Molecular biology grade (AOF not tracked)
Manufacturing	Facilities	Separate HVAC for upstream and downstream facilities Qualified cleanrooms—upstream process (cleanroom class D), downstream purification and formulation (class C) Animal origin-free (AOF) Beta-lactam-free environment	HVAC systems for downstream facilities Qualified cleanrooms for purification/formulation processes (class D) Upstream—standard laboratories Shared processes based on animal origin and beta-lactam	HVAC systems for downstream facilities Qualified cleanrooms for purification/formulation processes (class D) Upstream—standard laboratories
	Equipment	Closed single-use system (fermenters, bags, tubing) Dedicated TFF membranes, purification resins	Shared upstream and downstream equipment Buffer exchange in open containers using standard dialysis	Shared upstream and downstream equipment Buffer exchange in open containers using standard dialysis
	Fermentation media	AOF rich semi-synthetic media Single-use fermentation vessels	Steel tank, shared equipment fermentation Standard complex media	Steel tank, shared equipment fermentation Standard complex media
	Purification	Single-use columns and resins for enzyme manufacturing Dedicated columns and resins for NTP manufacturing	Multi-use columns and resins	Multi-use columns and resins
	Process	Validated for each product	Validated for product families	Validated for product families or not validated

Table 2. TheraPure reagents portfolio for commercial applications.

In vitro transcription enzymes	Nucleotides	Phosphoramidites
Restriction enzymes T7 RNA polymerase Inorganic pyrophosphatase DNase I Capping enzymes 2’-O-methyltransferease Poly(A) polymerase Ribonuclease inhibitor T7 enzymes mix	NTPs (ATP, CTP, GTP and UTP) Modified nucleotides (modified UTP and CTP) ARCA, cap analog, and custom cap analogs NTP mix NTP/ARCA/cap mixes	DNA phosphoramidites RNA phosphoramidites 2’-O-methoxy-ethyl (MOE) phosphoramidites 2’-O-methyl (OMe) phosphoramidites 2’-Fluoro phosphoramidites Dye-labeled phosphoramidites

Manufacturing scale-up to serve a global market

To better serve the growth in nucleic acid therapeutic development, we made significant investments in operational expansion with a new industrial scale manufacturing facility at our Bioscience Center of Excellence in Vilnius, Lithuania. And we’ll continue to invest so we can deliver leading innovation, support, and manufacturing capabilities to help accelerate your work.

Purpose-built facility (5300 m²) for large-scale production of TheraPure reagents
Manufacture and quality processes meet regulatory standards (following cGMP principles)
Backed by more than 4 decades of enzymes and nucleotides manufacturing experience

Purpose-built facility for IVT enzymes and nucleotides for mRNA therapeutics

Figure 1. Bioscience Center of Excellence in Vilnius, Lithuania. Certification status: ISO 9001, ISO 13485.

Expertise and support at every step of the way

Our goal is to support you at every stage of the nucleic acid therapeutic development process. We offer integrated solutions across the workflow, custom capabilities, and the ability to scale with you as your project grows. Our skilled team from technical support staff to business development managers partner with your project team, providing the support you need to see your project to completion (including product customization, regulatory documentation, and more).

We recognize that as a critical raw material supplier, we play an important role in supporting your need for high-quality products, a stable supply chain, and robust risk mitigation strategies. Our network of manufacturing facilities enables us to supply high-quality products to our customers globally. Redundant manufacturing helps maintain that supply without interruption. Our sites are audit-ready, hosting hundreds of customer site audits per year.

headphones icon