New enzyme variants developed by Codexis may have better efficacy than enzymes currently used for enzyme replacement therapy in patients with Pompe disease and other diseases, according to preclinical data presented at the American Society of Gene and Cell Therapy (ASGCT) 25th Annual Meeting. 

The engineered acid alpha-glucosidase (GAA) enzyme variants for Pompe disease retained more than 60% of their activity in plasma at 37 oC for 50 hours, the company reported. In comparison, wild-type GAA maintains less than 10% activity for 24 hours under the same conditions.

Researchers also reported that fibroblasts obtained from patients with Pompe disease that were grown in culture and myoblasts missing the GAA gene that were treated with some of the new enzyme variants had around 40 times more enzyme activity than wild-type GAA. 

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The new enzyme variants have been developed as part of Codexis’ gene therapy programs and are administered as transgenes. The company also engineers enzymes for hemophilia A and Fabry disease.

Read more about enzyme replacement therapy for Pompe disease

Codexis’ president and chief executive officer, John Nicols, said in a press release from the company, “The exciting results coming out of our early-stage programs across Hemophilia A, Fabry Disease, and Pompe Disease showcase the promise of engineered enzyme variants to inspire a new generation of gene therapies with improved stability and expression profiles.”

The enzymes are engineered using Codexis’ CodeEvolver® platform, which allows structure-function analyses of a large number of enzyme variants to select the ones that are superior to the naturally occurring enzymes used today.

“When applied to gene therapies, this process holds great potential for addressing unmet needs and improving patient outcomes, and we look forward to further advancing these programs as we work to harness the untapped potential of directed evolution,” Nicols said.

The meeting took place from May 16 to May 19, 2022, in Washington, DC and virtually.


Codexis presents pre-clinical data highlighting gene therapy programs at the ASGCT 25th Annual Meeting. News release. Codexis, Inc; May 16, 2022.