Cisterna Biologics

Cisterna Biologics is a technology company. It aims to solve the main challenges currently facing the biotech industry to develop mRNA-based therapeutics – quality, quantity, longevity and cost of mRNA. As mRNA technology matures, it becomes imperative that these issues are solved so we can fully explore mRNA's endless possibilities as a therapeutic.

Context:

Many of you likely had mRNA vaccines to protect against COVID-19 - but how many of you know that mRNAs are being developed into other cutting edge, life-saving therapeutics? It is very likely that a large portion of the future treatments that you and I take for a number of ailments will be in the form of mRNA-based therapeutics. The range of diseases that mRNA promises to treat include heart disease, liver dysfunction, solid tumors, blood cancers, and several genetic disorders.

Problem:

For therapeutic applications, the quality of the mRNA needs to be extremely high compared to mRNA used for vaccines. For example, one of the well-known contaminants, double-stranded RNA (dsRNA) is present in trace amounts alongside mRNA but it does no harm at the fractional doses in mRNA vaccine (micrograms). However, higher and repeat dosage (milligrams) of the same, as applied to other mRNA applications and treatments, can potentially have devastating consequences if we do not remove the dsRNA first. Currently, Pharma companies spend millions of dollars to remove dsRNA by employing multiple chromatography purification systems. Unfortunately, these processes add to the cost of production of single chromatography purifications and lead to substantial wastage of mRNA, thereby resulting in poor yields - the latter adding even more to the costs of production.

Solution:

Cisterna uses proprietary technologies to either remove a contaminant at its source or replace the source itself. To remove dsRNA, we use ribozymes (molecular scissors) to precisely cut the mRNA at its 3’ end. This assures not only 3’ homogeneity, but also eliminates dsRNA, which are primarily produced due to self-templated additions at the 3’ ends. Utilizing a PCR-like system to amplify the DNA template in large quantities eliminates the requirement for plasmid enrichment in bacteria, the prime source of endotoxin contamination. Additionally, doing away with plasmids completely means a further reduction in extraneous dsRNA arising from cryptic promoter sequences in the undigested non-template strand. These are just a few examples of Cisterna’s powerful technologies being used to achieve our goal of 10x higher quality mRNA for therapeutic application.

Founder:

Hari Bhaskaran completed his Ph.D. at UT-Austin under the mentorship of Dr. Rick Russell; his thesis was published in the prestigious journal Nature. He has held positions of increasing responsibilities in both academia and industry. His roles have led him to produce innovative mRNA construct designs for therapeutics, create scale-up techniques for manufacturing and improve process development for purifications and analytics. He is the author of several publications and industry patents.

Asks:

If you’d like to more about Cisterna’s high-quality mRNA, please feel free to reach out to founders@cisternabx.com