New preclinical data confirming the effects of GalNAc-conjugated SERPINA1 AIMers in restoring the production of functional alpha-1 antitrypsin (AAT) protein in the serum of a mouse model of AAT deficiency (AATD) were recently presented at the TIDES USA: Oligonucleotide & Peptide Therapeutics Conference. 

Previously, researchers had reported that the SERPINA1 AIMers led to around 60% editing of SERPINA1 messenger RNA (mRNA) as well as 5-fold greater levels of circulating AAT in the serum of the animals.

The functionality of the restored AAT protein was measured by a 3-fold increase in the inhibition of neutrophil elastase compared to that of a placebo. Moreover, there was a reduction of liver aggregates in the animals following SERPINA1 AIMer treatment.

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“Alpha-1 antitrypsin deficiency (AATD) is uniquely suited for an RNA editing therapeutic,” Paul Bolno, MD, MBA, president and chief executive officer of Wave Life Sciences, said in a press release. ”Our AATD program is rapidly advancing towards clinical development with [Investigational New Drug] enabling studies on track to initiate in the third quarter of this year.”

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According to the press release, the company expects to select an AATD AIMer development candidate and start toxicology studies soon to enable an IND application.

AIMers are A-to-I editing oligonucleotides that recruit endogenous adenosine deaminase acting on RNA (ADAR) enzyme to correct the Z mutation in the SERPINA1 mRNA, thereby increasing levels of circulating functional AAT protein to therapeutically meaningful levels. Wave Life Sciences is developing the AIMers using its PRISM™ platform.

AATD is caused by mutations in the SERPINA1 gene that disrupt the normal production of AAT protein. AAT is normally synthesized in the liver and released into the bloodstream to be carried to the lungs. Here, it acts as an inhibitor of the neutrophil elastase enzyme and protects the alveolar walls from the enzyme’s damaging effects.


Wave Life Sciences reports first quarter 2022 financial results and provides business update. News release. Wave Life Sciences Ltd; May 12, 2022.