The two posters demonstrate in vivo superiority of circular RNA vs. linear mRNA-based expression.
“Circio has generated results demonstrating that the circVec 2.1 design performs very well in vitro. We have now confirmed this in vivo with statistically significant higher expression level and durability for circVec 2.1 DNA vectors compared to standard linear mRNA-based expression,” said Dr Thomas Hansen, chief technology officer at Circio.
“These results provide an important technical proof-of-concept for Circio’s technology platform in an animal model. We now have confirmation for our expectation that this could translate into improved gene therapies for patients in the future.
“In recent experiments, Circio has observed up to four months circVec durability in vivo. This substantially outperforms mRNA vector expression. Following these results, we can rapidly advance to design and test circVec in several AAV and DNA-based vectors. This will validate these very promising data in therapeutically relevant formats.”
At ASGCT, Circio also presented its dual-function ‘remove and replace’ concept for Alpha-1-antitrypsin deficiency (AATD).
AATD is a genetic disease that causes severe symptoms in the lung and liver.
There are currently no robust therapeutic options available for this indication and the condition still represents a major unmet medical need, with over 200,000 patients affected in the USA and EU alone.
With the technologically differentiated circVec remove-&-replace format, Circio has developed a ‘unique’ gene therapy concept that it claims can deal with both the lung and liver-associated symptoms in one single therapeutic.
“AATD is a challenging genetic disease to treat. This is in part due to the two distinct pathologies in the liver and lung. We have now established and technically validated circVec constructs that can both replenish functional wild-type AAT and specifically remove more than 90% of the mutated protein,” said Dr. Victor Levitsky, chief scientific officer at Circio.
“This is challenging to achieve because the functional and mutant forms are very similar. By using circular RNA-based AAT expression, Circio is uniquely able to separate the two species for mutant-specific knockdown, thereby solving two problems with one single product.”
