Thermo_Apr2021_The_mRNA_TherapeuticsBoom - 2

The mRNA Theraptutics Boom	
is back in focus with the general acknowledgment
that these types of therapies do not target and manipulate genes and DNA.
To date, no mRNA-based therapy has been commercialized though some are in late-stage trials or
approved for emergency use, such as vaccines
targeting SARS-CoV-2. The vast majority of therapies
in development apply to relatively small populations,
thousands to hundreds of thousands of patients. Even
mRNA-based cancer immunotherapies would serve
a significantly smaller subset of patients than a global
vaccination campaign.
Since preclinical and early clinical pipelines of most
of these mRNA therapies only required a few liters
of materials, traditional laboratory-scale approaches,
such as precipitation, were leveraged for production.
" We are going to see mRNA therapies start to move
quicker to the clinic, " says Kelly Flook, PhD, Senior
Product Manager, Purification Products, Thermo
Fisher Scientific, " and a greater acceptance of protein
replacement therapies and varied immunological
approaches than are currently being evaluated. "

Scaling-Up Options
The drive to rapidly develop a COVID vaccine put a
focus on large-scale mRNA manufacturing. The limits
of research-scale purification techniques were realized,
and available purification methods became a bottleneck for commercialization.
To resolve this challenge, different options are under
investigation. For example, scaling up reverse-phase
chromatography is of interest. " It is scalable but not
as efficient as an affinity approach in purifying the
product and removing process impurities, " says Flook.
In addition, reverse-phase chromatography uses flammable solvents requiring the removal of detrimental
post-purification impurities. Safety is a concern, as well
as the necessity and expense of building a chemical
manufacturing site to handle the solvents.
" Aqueous-based techniques, ion exchange, and
affinity, are commonly used in research, and a similar
2 | GENengnews.com

solution is desirable for scale-up production of mRNA, "
says Flook. Process speed also plays an important role.
" A few years ago, as more companies began working
on therapeutics in this space, we saw an increase in
inquiries about large-scale mRNA purification, " says
Flook. " Most resins on the market were research-scale
technology, such as our popular Dynabead option
with a polyT on the surface. Initially, we provided
custom resins until the momentum grew, and it made
sense to develop a generic product. So we took the
polyT technology and applied it to our bioprocessing
POROS™ resins. "

Producing mRNA
" RNA is made using a process called in vitro transcription (IVT). During the IVT process, DNA is converted
to RNA, " explains Venkata Indurthi, PhD, Vice President, Research and Development, Aldevron. " It is
critical to get rid of all the impurities after the reaction is complete, including any residual raw materials, because they can trigger nonspecific immune
responses. "
Compared to DNA, RNA is fragile; harsh purification
techniques are unsuitable. RNA also has secondary
structures that can impact purification.
" There are multiple ways of purifying RNA, chargebased methods, precipitation-based methods, and
others like hydrophobic interaction chromatography
(HIC), " says Indurthi. " The specific advantage of the
affinity oligo dT approach is that you can easily get rid
of the impurities generated during IVT. "
Affinity chromatography, a highly-scalable method,
has earned its credits in the development of biologics,
such as the use of Protein A for the purification of therapeutic antibodies and, more recently, anti-AAV resins
in gene therapy workflows. An effective affinity purification step can help to simplify biomolecule downstream processing, reduce the number of purification
steps, and lower the overall cost of goods in biotherapeutic manufacturing.
Thermo Fisher's new affinity-based mRNA chroma-



https://www.thermofisher.com/us/en/home.html https://www.genengnews.com

Thermo_Apr2021_The_mRNA_TherapeuticsBoom

Table of Contents for the Digital Edition of Thermo_Apr2021_The_mRNA_TherapeuticsBoom

Thermo_Apr2021_The_mRNA_TherapeuticsBoom - 1
Thermo_Apr2021_The_mRNA_TherapeuticsBoom - 2
Thermo_Apr2021_The_mRNA_TherapeuticsBoom - 3
Thermo_Apr2021_The_mRNA_TherapeuticsBoom - 4
Thermo_Apr2021_The_mRNA_TherapeuticsBoom - 5
https://www.nxtbookmedia.com