In this interview, our experts address questions on our new mRNA Research Services and how they can help to accelerate the development of mRNA and/or encapsulation projects, with maximum efficiency via in-silico codon optimization.
Q: Which development stage is supported by Lonza’s mRNA Research Services?
This offering is designed for companies that are in the research and discovery stages of their development project(s).
If you are in this stage and have identified what kind of protein you would like to encode by mRNA and which tissue or cells you want to deliver the mRNA to, then you will likely benefit from our new mRNA Research Services.
Q: What is included in Lonza’s mRNA Research Services?
We work with our clients to deliver a bespoke offering of mRNA Research Services that are built around your specific development needs. This can include an end-to-end solution, or a tailored package that only delivers what you need during your mRNA development or LNP encapsulation project.
Our comprehensive mRNA Research Services include:
- Providing an mRNA backbone with full freedom to operate
- Designing an efficient mRNA sequence for your protein using in-silico codon optimization. This takes manufacturability, stability and protein expression into account
- Manufacturing small amounts (microgram range) of multiple different mRNA constructs based on in-silico codon optimization. This manufacturing can use either all-natural
- Physico-chemical testing of these mRNA constructs (e.g. integrity, dsRNA) and early stability testing
- Testing of the protein expression profile and duration of the expression (mRNA stability)
- Immunogenicity testing services for both innate and adaptive immune responses of these mRNA constructs in human ex-vivo immune cells
Once the above steps have been completed by our specialist mRNA research team, we can then recommend which mRNA construct to take forward for pharmacological testing. This will be followed by:
- Manufacturing of 100-120 mg of Research Use Only (RUO) material for a selected mRNA construct
- Physico-chemical testing of RUO material (extensive list of parameters including endotoxin and bioburden)
- Potency testing of RUO material
Q: What is included in the service offering for LNP encapsulation?
To help you avoid the cumbersome shipment processes involved with moving mRNA across sites and borders, we provide end-to-end LNP encapsulation alongside our mRNA Research Services.
This service offering is similarly customizable to suit your specific project needs, and can be a comprehensive support package or a bespoke selection of services. Our offering includes:
- Providing standard lipid pre-mixtures for LNP manufacturing for certain applications (e.g. delivery to the liver or as a prophylactic vaccine) as of Q4 2024
- Encapsulation of the RUO mRNA manufactured by Lonza or other nucleic acids provided by you using the selected lipid pre-mixture
- Analytical testing of your RUO LNP-encapsulated nucleic acids (extensive list of parameters including e.g. Size/PdI, EE, Integrity, Lipid Content/ID/Purity, CryoEM and more)
The extensive analysis of your LNP-encapsulated mRNA also includes:
- Potency testing
- Stability testing
- In vivo testing for the evaluation of biodistribution
- Immunogenicity testing services
Q: Is the development and manufacturing of an LNP-encapsulated mRNA less or more expensive than that of a mammalian protein?
Once you have identified a protein as a potential therapeutic, the question arises whether it would be better to administer this protein as a protein, or encode the protein using mRNA and administer the mRNA instead.
There are differences between both modalities with respect to biodistribution (e.g. intracellular vs. extracellular), immunogenicity, stability and others. If after thorough consideration both options are possible, then it is a valid question whether the development and manufacturing of an mRNA is less expensive than that of a protein.
The answer will depend on the protein and its manufacturing process (e.g. microbial vs. mammalian), but in general, the mRNA route should be less expensive as one molecule of mRNA can encode for multiple molecules of protein, which allows lower doses. In addition, it is easier to use a standardized manufacturing process for mRNA than for proteins, which likely reduces development timelines and costs.
Q: How are the results of mRNA Research Services delivered to clients?
In alignment with your bespoke service package, we will provide you with a detailed report containing all the necessary information for your product development and characterization. We strive for open communication and effective collaboration during the development of your product.
Q: Does Lonza offer encapsulation services aside from mRNA?
We not only offer the LNP encapsulation and in-silico codon optimization of mRNA or related molecules such as circular RNA or self-amplifying RNA, but also LNP encapsulation of short RNAs such as siRNA as well as DNA.
The common denominator should be the possibility of using similar analytical methods for the molecules to be encapsulated, which is the case for nucleotides. This ensures time- and cost-efficient delivery of your material, as the lengthy development of new analytical methods is not necessary.
It’s worth noting that at Lonza we currently only manufacture different versions of long RNA, such as mRNA, circular RNA and saRNA. We do not have dedicated facilities for the manufacturing of oligonucleotides or DNA.
Q: How does a small biotech company benefit from Lonza’s mRNA Research Services?
Our mRNA Research Services allow you to jump-start the development of LNP-encapsulated mRNAs without hiring your own experienced chemistry, manufacturing and controls (CMC) team for this modality.
Our extensive experience in cGMP manufacturing also ensures you start in the research phase already having the end in mind. This includes having a robust and scalable process, a stable molecule with high manufacturability, and a low risk of immunogenicity.
Taking this approach contributes to the acceleration of your project, as well as maximizing the probability of success. It will also minimize your internal workload, which allows you to focus on your core activities.
Q: How long does it take to get the encapsulated oligonucleotide for in vivo testing?
At Lonza, we can deliver this end-to-end mRNA Research Services and LNP encapsulation package in as little as 18 weeks:
Q: Keen to learn more about Lonza’s mRNA Research Services?
If you think that this service offering is exactly what your project needs, or you’re looking to fast-track the development of your LNP-encapsulated mRNA with maximum efficiency via in-silico codon optimization, our experts are here to help.