How Do You Make Custom mRNA for Research, From Sequence to LNP?
From sequence design to LNP formulation: the steps in producing research mRNA, where experiments can go wrong, and the Cypher AI Marketplace providers that support each stage.
By Cypher AI ·
Getting a cell to make a protein from mRNA takes more than the protein's sequence. The mRNA has to be designed, made, cleaned up and usually packaged before it goes into cells or animals. Each of those steps can affect protein expression.
When protein expression is lower than expected, the problem may arise at any stage. The sequence may express poorly, residual impurities may trigger an antiviral response, or the formulation may fail to deliver enough mRNA into cells.
WHAT STEPS DOES IT TAKE TO MAKE mRNA FOR AN EXPERIMENT?
Making mRNA for an experiment takes four steps: design, transcription, purification and formulation. First, the sequence is designed. That covers the coding sequence and the untranslated regions (UTRs) on either side of it.
Next, the design is built as a DNA template, and an RNA polymerase copies it into mRNA outside the cell. This is called in vitro transcription, and it usually adds a 5' cap and a poly(A) tail. The mRNA is then purified and checked. For most work in animals, it is also packaged into lipid nanoparticles (LNPs) before dosing.
WHY DOES THE mRNA SEQUENCE MATTER?
The sequence decides how much protein each mRNA molecule makes and how long the molecule lasts. Most amino acids can be encoded by more than one codon, so one protein can be written as a very large number of different mRNA sequences. The UTRs on either side add more choices.
Those choices change expression and stability. They can also change which cells make the most protein, which matters when lipid nanoparticles reach the liver as well as the cells you meant to target.
This design step is what nCode Biosciences works on. nCode is an AI company that designs mRNA sequences for expression, cell-type targeting and stability. You give nCode a protein or mRNA sequence and your goals, and it returns a ranked list of full-length redesigned constructs. nCode aims for more than 5x higher expression in the cell type you choose, and more than 5x lower expression in an off-target cell type you choose.
WHY DOES PURIFICATION MATTER FOR IN VITRO TRANSCRIBED mRNA?
Purification matters because in vitro transcription also makes small amounts of double-stranded RNA (dsRNA). Cells treat dsRNA as a sign of viral infection. They respond by switching on interferon signaling and slowing translation, which reduces protein expression.
Removing dsRNA makes a large difference. In a 2011 study in Nucleic Acids Research, Katalin Karikó and colleagues found dsRNA in every in vitro transcribed sample they tested. After they removed it by HPLC, mRNA made with modified nucleosides triggered no interferon or inflammatory cytokine response. It was also translated at 10 to 1,000 times higher levels in primary cells.
Impurities matter even more when an experiment calls for higher or repeated doses, because immune activation and tolerability become bigger questions. That's why it helps to ask for dsRNA results with every batch.
WHAT DOES LNP FORMULATION ADD?
LNP formulation protects the mRNA and carries it into cells. A lipid nanoparticle is a small particle of lipids that wraps around the mRNA, and the approved mRNA vaccines are delivered this way. Two measurements tell you whether a batch is usable: particle size, and encapsulation efficiency, which is the share of the mRNA that ends up inside the particles.
ARNAV Biotech, an mRNA manufacturer in Atlanta, handles both synthesis and formulation. It makes custom and catalog mRNA and packages it into LNPs. Because one team runs both steps, the QC data for the mRNA and the LNPs comes from the same lab. That makes it easier to trace the cause when expression is lower than expected.
WHICH PROVIDERS ON THE CYPHER AI MARKETPLACE COVER THESE STEPS?
As of October 2026, nCode Biosciences and ARNAV Biotech cover design, synthesis and formulation on the Cypher AI Marketplace. The two companies also work together. In 2026, ARNAV named nCode its AI mRNA design partner.
nCode lists two services at $2,500 each. Sequence optimization has an estimated turnaround of 3 to 21 days. Library screening takes a set of UTR and coding-sequence designs and ranks them for synthesis and screening, in 1 to 7 days.
ARNAV lists mRNA synthesis and LNP formulation, both priced by quote. The listings estimate 3 to 30 days for mRNA and 5 to 30 days for LNPs.
FREQUENTLY ASKED QUESTIONS
What QC should I ask for with research mRNA? For the mRNA, ask for capping efficiency, dsRNA and endotoxin results. For an LNP batch, ask for particle size and encapsulation efficiency. ARNAV's website lists each of these tests.
Do I need modified nucleosides? Many teams use them. In the 2011 Karikó study, modified nucleosides lowered the immune response, but only mRNA that was both modified and purified avoided it fully. ARNAV makes mRNA with modified bases.
Do I need to supply a DNA template? No, but supplying one speeds things up. The template is the DNA that the RNA polymerase copies into mRNA. ARNAV can have custom mRNA ready in as few as 3 business days when you send the template.
HOW DO YOU ORDER mRNA DESIGN, SYNTHESIS AND LNP FORMULATION ON CYPHER AI?
You can browse the nCode and ARNAV listings at cypherbio.ai/services without an account. To order, create a free Cypher AI account. nCode's services have a listed price, so you can order the design directly. ARNAV sends a quote for synthesis and formulation, and you pay each provider directly.
When you order from a Cypher AI project, each order records the project, ELN entry and LIMS samples it came from. That keeps the design, the mRNA batch and the LNP batch tied to the experiment they were for.