Intellia demonstrates efficacy of gene therapy in preclinical models

By The Science Advisory Board staff writers

Intellia Therapeutics has demonstrated that physiological protein levels of human alpha-1 antitrypsin (AAT) in nonhuman primates can be achieved following a single administration of its in vivo gene therapy.

In the nonhuman primate study, the company achieved normal AAT protein levels following targeted insertion of the human SERPINA1 gene, which remained stable through at least 11 weeks.

The SERPINA1 gene normally encodes the AAT protein produced in the liver that is then secreted to protect the lungs. SERPINA1 mutations can cause AAT deficiency, a rare, genetic disease that commonly manifests in lung dysfunction, as well as in liver disease in some patients.

The company is developing several CRISPR/Cas9-based genome editing strategies to treat lung and liver manifestations of AAT deficiencies, which occur due to mutations in the SERPINA1 gene. Intellia's targeted in vivo insertion platform uses a hybrid delivery system combining a nonviral lipid nanoparticle, which encapsulates CRISPR/Cas9 components, with an adeno-associated virus carrying a donor DNA template to enable therapeutic protein production.

The company is also investigating a consecutive genome editing approach where the PiZ allele – the most common disease-causing mutation of SERPINA1 -- is knocked out and the normal human SERPINA1 gene is inserted.


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