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OVERCOMING mRNA PRODUCTION SCALE-UP CHALLENGES
5. Keep GMP in mind
There are many IVT kits that can be invaluable when
beginning RNA development, but these will contain
components of animal origin. When beginning to
scale up, it's a good idea to move early to materials
suitable for GMP manufacturing early, meaning
process development is completed with the same
raw materials and formulations, allowing a quick
transition to GMP manufacturing. As you scale up,
some aspects will change, but ensuring consistency
in as many areas as possible will result in a smoother
scale-up process. The use of GMP-grade materials
early minimizes the need for the costly and time-consuming
testing, auditing, and documentation needed
for changing materials. TheraPure GMP nucleotides
and enzymes are designed for seamless scale-up of
your mRNA synthesis with scale, quality, consistency,
and regulatory needs in mind (Figure 3).
6. Secure a sufficient supply of DNA, or
consider going synthetic
The DNA template is a key critical raw material for
mRNA production. Due to an increased demand for
plasmid manufacture for mRNA and gene therapy
applications, supply can be limited, especially for
GMP-grade plasmid DNA. Before you begin to scale
up, you must ensure a sufficient and steady supply
of your DNA template for your desired output. At
Thermo Fisher Scientific, Patheon™ Pharma Services
offer cGMP-grade plasmid DNA for all stages of development
and commercialization, with capacity and
flexibility to scale with you.
Alternatively, you could look to synthetic options for
generating plasmid DNA, such as rolling-circle DNA
amplification approaches or Invitrogen™ GeneArt™
plasmid construction and purification services, to
mitigate against supply chain issues.
1
Plasmid DNA linearization
2
Restriction enzymes
Eam1104l
Linear DNA
IVT enzymes
T7 RNA polymerase
Nucleotides
ATP, CTP, GTP, UTP,
N1-Me-pUTP
Pyrophosphatase, inorganic;
RNase inhibitor
3
Post-IVT cleanup
Template digestion enzyme
DNase I
Figure 3. Overview of materials used in mRNA production.
GENengnews.com | 17
mRNA synthesis
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