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Chameleon’s immunomodulatory tech wins breakthrough award

Adeno-associated virus (AAV)-based gene therapy uses ‘gutted’ non-pathogenic viruses to carry good genes to cells to replace broken versions of the genes. However, normal immune responses to viruses limit gene therapies’ use to only a select number of patients in only some types of severe genetic diseases.

Chameleon said its EVADER platform suppresses immune responses to gene therapies by leveraging molecules used by some tumor cells to evade immune detection and activation.

Therefore, the technology can help populations who currently cannot receive AAV gene therapies, he continued. Examples include children with fatal genetic diseases who need repeat doses of gene therapy because their organs are still growing, children and adults with prior exposure to AAV in their lifetimes, and gene therapy clinical trial participants who received an insufficient dose of gene therapy during their first treatment.

EVADER particles consist of a lipid membrane coated with immune suppressive proteins that deliver signals to allow gene therapies to get past the immune system. “By packaging AAV DNA carriers in protective lipid membranes, EVADER shields them from existing antibodies. Two naturally occurring human proteins attached to the lipid envelope also act as ‘checkpoint immune suppressors’ to prevent new antibody formation and T-cell activation.”

Testing

In animal models, the biotech said EVADER is proving to be very effective: not only does it overcome the immune response to AAV, but gene therapies that contain EVADER are more potent at delivering their transgene payloads.

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