IVT RNA and LNP Manufacturing

VectorBuilder offers a full-service platform for in vitro transcription (IVT) RNA synthesis and lipid nanoparticle (LNP) encapsulation, streamlining the development of your RNA therapeutics every step of the way. Drawing on our expertise in RNA therapeutics development, our CDMO team of RNA experts excels in providing optimal personalized IVT vector design (e.g. sequence optimization) and LNP encapsulation solutions (e.g. customizable formulation, antibody conjugation) that enhance efficacy, safety, and manufacturability of RNA therapeutics.

Highlights

Comprehensive Platform Expertise encompassing RNA therapeutic preclinical development, process development, and GMP manufacturing.

Fully Customizable and Scalable Versatile platform supporting mRNA, saRNA, circRNA, and LNP development needs, from research to commercial purposes.

Highest Quality and Consistency State-of-the-art GMP facilities and equipment providing the highest purity and consistency.

Grades of IVT RNA Offered

We produce IVT RNA in several grades to cover a full range of downstream applications including drug discovery research, preclinical studies, clinical trials, and commercialization.

R&D

Preclinical

Clinical

Commercial

Research-grade

GMP-like

GMP-grade

Suitable for basic research and drug discovery studies
Produced under standard laboratory conditions with stringent QC

Suitable for preclinical studies (e.g. animal testing of drug safety and metabolism)
Produced in PAS or GMP facilities in a manner that adopts key features of GMP guidelines
Can be produced under RNase-free fermentation and purification conditions

Suitable for preclinical studies, clinical studies, and commercialization
Produced in our certified GMP suite with strict adherence to GMP guidelines
Includes comprehensive QC assays and batch release report

Comparison of different grades of IVT mRNA

	Research-grade	GMP-like	GMP-grade
Applications	Basic research, drug discovery, preclinical studies	Preclinical studies such as animal testing of drug safety and metabolism	Preclinical studies, clinical studies, and commercialization
Production scales	mRNA: 0.1-10 mg LNP: 0.1-3 mg	mRNA: 0.01-20 mg LNP: 3-20 mg	mRNA: 50 mg - 2 g LNP: 50 mg - 2 g
Quality system	ISO9001	ISO9001 while adopting key features of GMP system	ICH quality guidelines for GMP manufacturing
Production facility	In parallel production in shared laboratory space	Production in segregated suites	Production in certified GMP suites
Document control and traceability	No	Yes	Full traceability
QC and release	Standard QC	Performed on a case-by-case basis depending on individual project needs (see below)	Full panel QC assays and analytical development based on individual project needs
Aseptic fill/finish	N/A	Available upon request	Yes
Storage of retention sample	Available upon request	Available upon request	Yes
Other deliverables	COA	1. COA 2. Manufacturing summary 3. TSE/BSE certificate upon request	1. COA 2. TSE/BSE certificate 3. CTD documents 4. Others (BMR, etc.) upon request

Workflow for Production of GMP IVT mRNA

VectorBuilder strives to deliver high quality RNA products in a time-effective manner. Here is a typical GMP production workflow of IVT mRNA:

Vector
Characterization

Process
Development

Cell
Banking

Plasmid
Production

RNA & LNP
Production

QC & Release

IVT vector design
and cloning

USP/DSP
development
for plasmid,
mRNA, and LNP
Analytical
development

Segregated
suite
(GMP-like)
GMP suite
(GMP-grade)

Closed system

General/physical
properties
Identity
Purity
Safety

Platform Technologies

Our manufacturing process offers cell-free production of IVT vector DNA that greatly shortens production time and innovative purification processes for efficient removal of impurities. With our commitment to innovation, we continuously refine our processes to stay at the forefront of RNA technology.

Cell Bank recovery and culture > Fermentation > Harvest and alkaline lysis > Centrifugation > Chromatography > TFF > Sterile filtration > QC

Plasmid DNA
linearization

In vitro
transcription
(IVT RNA production, co-
or post-transcriptional
modifications)

Purification
(Chromatography)

Checkpoint QC

LNP encapsulation
(Rapid phase mixing)

Formulation
(TFF, sterile
filtration, fill/finish)

End QC
and release

For more information on our manufacturing platform and/or GMP capabilities, contact the VectorBuilder service team.

Talk to Our Experts

Analytical Methods

Quality control assays

The list below summarizes our range of available QC assays for the release of GMP-like and GMP-grade IVT RNA products. Additional QC services not listed below may be provided upon request. Please contact our service team to determine the best QC package for your needs.

Talk to Our Experts

	Attribute		QC Assay
IVT Template Vector	General/physical properties	Plasmid concentration	Nanodrop
	Identity	Plasmid size	Restriction digestion
		Full-length plasmid sequence	Sanger sequencing
			NGS
			Third-generation sequencing
IVT RNA	General/physical properties	Appearance	Visual inspection
		pH	pH meter
		mRNA concentration	Nanodrop
		mRNA concentration	RiboGreen assay
	Potency	Protein translation	In vitro translation followed by Western blot
	Potency	Transgene expression	Cell transfection
	Identity	mRNA sequence	Reverse transcription followed by Sanger sequencing
		mRNA length	Denaturing agarose gel electrophoresis
		mRNA length	Capillary gel electrophoresis
	Purity	OD260/280	Nanodrop
		mRNA integrity	Denaturing agarose gel electrophoresis
		mRNA integrity	Capillary gel electrophoresis
		Capping efficiency	LC-MS
		PolyA analysis	LC-MS
		Residual dsRNA	Dot blot assay
		Residual plasmid DNA	qPCR
		Residual protein	NanoOrange assay
		Residual solvents	Gas chromatography
	Safety	Sterility	Bioburden test
		Mycoplasma	Culture method
		Mycoplasma	qPCR
		Endotoxin	Kinetic chromogenic assay (KCA)
LNP-encapsulated RNA and Plasmids	General/physical properties	Appearance	Visual inspection
		Concentration	RiboGreen assay
		pH	pH meter
	Identity and purity	Encapsulation efficiency	RiboGreen assay
		Particle size	Dynamic light scattering (Zetasizer)
		Polydispersity index (PDI)	Dynamic light scattering (Zetasizer)
		Surface charge (Zeta potential)	Dynamic light scattering (Zetasizer)
		Encapsulated RNA integrity	Capillary gel electrophoresis
	Safety	Sterility	Bioburden test
	Safety	Endotoxin	Kinetic chromogenic assay (KCA)

Stability studies

Drug stability studies are performed following ICH guidelines. Forced degradation studies are performed to evaluate the influence of light, temperature, pH, etc., on the quality attributes of IVT RNA.

Our Facilities

VectorBuilder currently has about 100,000 ft² of modern GMP-compliant facilities with advanced designs and state-of-the-art equipment meeting GMP regulations of US, EU, Japan, China, and PIC/S. Our facilities comply with ICH guidelines and are suitable for GMP production for Phase I/II/III clinical trials.

GMP Manufacturing
Suites
Fill/finish Suites
QC Laboratories
GMP Warehouse

Our new RNA-focused GMP facility is equipped with state-of-the art equipment and has been meticulously designed to prioritize flexibility and adaptability to cater to custom project requirements.