Biomanufacturing · RNA production
Cisterna Biologics
A very small San Diego County company sells research grade RNA off a price list while three federal Phase I grants test whether its purification chemistry can reach the purity that mRNA medicines will demand. No clinical program, no FDA registration, no priced round on record.
A 976 nucleotide molecule for $45
The product page is plain. Catalog number CR55, enhanced green fluorescent protein mRNA, 976 nucleotides, four day lead time, $45. Below it, CR109, human erythropoietin mRNA, 838 nucleotides, $65. Below that, CR108, an mRNA encoding the machine designed gene editor OpenCRISPR-1, 4,459 nucleotides, $165. Invoices go out on Net30 terms.
About thirty RNAs are listed the same way: bacterial transfer RNAs, fluorescent aptamers, flexizymes, four messenger RNAs. Most of the short ones sit at $132. It reads like a chemical supply catalog, which is the point. Cisterna Biologics is not developing a drug. It sells the molecule other people need in order to develop one, and it argues that the molecule most of them buy today is dirtier than they think.
What comes out of the tube besides mRNA
Almost all mRNA is made by in vitro transcription: a DNA template, an RNA polymerase, a pool of nucleotides, a few hours. The reaction is not clean. The polymerase drops off early and leaves truncated fragments. It copies the newly made strand back onto itself and produces double stranded RNA. It adds extra nucleotides past the intended end. Some transcript stays stuck to its DNA template.
Double stranded RNA matters most, because the innate immune system evolved to detect that shape. A 2025 review in the Journal of Chromatography A surveyed every published removal strategy and concluded the impurity is still not fully solved. A 2025 study from Sartorius BIA Separations and TRON in Mainz showed the other half: strip it out and protein output rises while innate immune activation falls. Dose is what turns a nuisance into a liability. A Covid vaccine delivers micrograms once or twice. Protein replacement therapy delivers milligrams, repeatedly, for years.
A ribozyme chemist starts a company
Hari Bhaskaran did his doctorate at the University of Texas at Austin in Rick Russell’s laboratory, on how catalytic RNAs fold, misfold and get rescued. In October 2007 the two published in Nature on CYT-19, a DEAD-box protein that unfolds both the correct and the misfolded forms of a group I ribozyme and lets the molecule try again. Nature ran a commentary on it in the same issue. He moved into industry afterward and worked on mRNA construct design, manufacturing scale up and purification.
Cisterna was incorporated in 2022 and joined Y Combinator’s Summer 2022 batch. The founding idea came straight out of the thesis work. If ribozymes are molecular scissors, use them: cut the mRNA precisely at its 3’ end so every molecule finishes in the same place, which also removes the self templated additions that generate double stranded RNA. Amplify the DNA template with a PCR like system instead of growing plasmids in bacteria, and the endotoxin problem leaves with the bacteria. The stated goal was “10x higher quality mRNA for therapeutic application”.
Three grants, three different bets
The government money arrived first, and not for a single idea. In August 2024 the National Science Foundation awarded a $274,980 SBIR Phase I, number 2415711, to test whether yeast could be turned into an mRNA factory, at “1/10th the cost of current systems”. That project closed in January 2026, and its Project Outcomes Report is the most useful document in the public file. Cisterna engineered Pichia pastoris to make a target mRNA and built a sequence guided capture and release step that pulled it out of thousands of native yeast transcripts. The purified product then made a fluorescent protein in human cells.
Two NIH Phase I awards followed in 2025, each attacking purity from a different direction. In June, NIGMS put $350,000 into an STTR to develop cold adapted RNA polymerases with UT Austin, on the theory that a polymerase running cold makes fewer byproducts. In August, NCATS put $349,746 into an SBIR to eliminate length impurities and then measure the immune response in mice.
What is proven, and what is still claimed
| Evidence | What the record shows | Source type |
|---|---|---|
| NSF SBIR 2415711 | $274,980, Aug 15, 2024 to Jan 31, 2026. PI Hari Bhaskaran. Completed. Outcomes report: engineered Pichia pastoris, sequence guided capture and release, protein expression in human cells. | Public record |
| NIH STTR R41GM159477 | NIGMS, $350,000, Jun 2025 to May 2027. Cold adapted polymerases with UT Austin, paired with the SPECC step. | Public record |
| NIH SBIR R43TR005424 | NCATS, $349,746, Aug 2025 to Jul 2027. Eliminate dsRNA, long and short truncated RNA, then test immunogenicity in mice. | Public record |
| SBIR.gov firm record | Three Phase I awards, $974,726. Zero Phase II, conversion rate N/A. First award 2024. One employee. Registered in Oceanside, CA. | Public record |
| Peer reviewed output | One 2025 ACS Nano Med paper with the Afonin laboratory at UNC Charlotte, carrying a Carlsbad Cisterna affiliation. Nothing published on SPECC or the yeast platform. | Public record |
| Purity claim | SPECC is said to produce full length RNAs “approaching HPLC-level purity without the associated bottlenecks”. Supporting figures sit on the company blog. No third party comparison found. | Company-stated |
| Patents | The Y Combinator profile credits the founder with industry patents. Searches for Cisterna Biologics as assignee returned nothing. | Not found |
| FDA and clinical | No drug establishment registration, drug listing or device registration in openFDA searches on Sep 23, 2026. No registered trial. | Not found |
| Named customers | None named. The catalog and Net30 invoicing exist; the buyers are not public. | Not found |
| Location | Y Combinator says San Diego, SBIR.gov says Oceanside, CB Insights and the 2025 paper say Carlsbad. All three are San Diego County. | Sources differ |
Read plainly: the chemistry has cleared an independently reviewed bar three times, and one project finished with a concrete result. What has not happened is everything after that. No Phase II has converted, no peer reviewed paper describes SPECC, and no customer has said in public that the RNA is better. The company asks to be judged on purity, and purity is the one thing the public record cannot yet check.
What to watch
- A Phase II award on any of the three projects. Three Phase I grants and zero Phase II is the number that decides the next two years.
- A peer reviewed SPECC result, or a head to head against ion pair reverse phase chromatography, the current reference method.
- A first named customer, or a move from research grade catalog RNA toward GMP material.
- The mouse immunogenicity data promised in the NCATS award, due by July 2027.
- Any SEC Form D, which would be the first sign of a priced equity round.
In their words
“Cisterna uses proprietary technologies to build the next generation of mRNA, free of impurities, at a fraction of the price.”
Company launch post, Y Combinator, 2022 · Company
“For therapeutic applications, the quality of the mRNA needs to be extremely high compared to mRNA used for vaccines.”
Company launch post, Y Combinator, 2022 · Company
“Currently, Pharma companies spend millions of dollars to remove dsRNA by employing multiple chromatography purification systems.”
Company launch post, Y Combinator, 2022 · Company
“To our knowledge, this work provides one of the first demonstrations that yeast-produced and purified recombinant mRNA can drive visible protein expression in human cells.”
NSF Project Outcomes Report, award 2415711, 2026 · Public record
“In collaboration with the University of Texas-Austin, Cisterna’s approach involves the development of cold-adapted (psychrophilic) RNA polymerases (RNAPs), which maintain high activity at low temperatures and reduce byproduct formation.”
NIH STTR project summary, R41GM159477, 2025 · Public record
“SPECC (SPEcific Capture and Cleavage) is Cisterna’s flagship purification system and is currently available for mRNA only.”
Cisterna Biologics product FAQ, Sep 2026 · Company
“Although various efforts have been made to optimize IVT synthesis to minimize dsRNA formation, dsRNA impurities still cannot be fully resolved.”
Siew and Zhang, Journal of Chromatography A, 2025 · Independent
“Before embarking on downstream process development to remove dsRNA, it is crucial to optimize the upstream IVT process first to minimize the generation of dsRNA by-products.”
Review authors quoted by LCGC International, Apr 2025 · Independent
Related companies
Sources
- Public recordNSF award 2415711, abstract and Project Outcomes Report
- Public recordNIH RePORTER 1R41GM159477-01
- Public recordNIH RePORTER 1R43TR005424-01
- Public recordSBIR.gov firm portfolio 1994107
- Public recordNSF organisation profile, CISTERNA BIOLOGICS, INC.
- Public recordKinetic redistribution of native and misfolded RNAs by a DEAD-box chaperone
- Public recordNucleic acid nanoparticles and regulatory terminology
- Public recordopenFDA drug, label and device registration queries
- IndependentRemoving immunogenic dsRNA impurities after in vitro transcription: a review of chromatography strategies
- IndependentRemoving Double-Stranded RNA Impurities Using Chromatography
- IndependentReverse-phase chromatography removes dsRNA, fragments and residual template
- IndependentCisterna Biologics profile, headcount and funding
- IndependentCisterna Biologics profile, headquarters and total raised
- CompanyLaunch YC: Cisterna Biologics
- CompanyCompany page and founder biography
- CompanyTechnology page, PRIME and SPECC
- CompanyOff-the-shelf RNA catalog and product FAQ
- CompanyRNA Purity and why it matters
- CompanyCisterna Completes NSF SBIR Phase I Yeast based mRNA synthesis Project
- CompanyCisterna Biologics home page, 2024 archive
Profile researched and written by Healthcare Discovery. Last updated September 29, 2026.
