BioCentury
ARTICLE | Distillery Therapeutics

Inflammation

November 14, 2017 10:58 PM UTC

Cell culture studies suggest a synthetic gene circuit that produces an IgE-blocking protein in response to allergy-promoting cytokines could help treat allergy. The synthetic gene circuit, expressed in a microencapsulated HEK cell line, was engineered to detect IL-4 and IL-13 as inputs via constitutive expression of a construct encoding IL-4 receptor, IL-13RA1and their shared downstream signaling molecule, STAT6, and to produce as an output a human IgE-blocking DARPin (designed ankyrin repeat protein via phosphorylated STAT6-dependent expression. In co-cultures with human whole blood, the microencapsulated engineered cells secreted more IgE-blocking DARPin in co-culture with blood from allergy patients than with blood from healthy volunteers. In co-cultures with blood from allergic patients plus an extract containing each donor's respective allergen, the microencapsulated engineered cells decreased IgE-triggered histamine release by basophils compared with a version of the cells lacking the DARPin-encoding construct. Next steps include testing the microencapsulated engineered cells in an animal model of allergy.

The Genentech Inc. unit of Roche and Novartis AG market Xolair omalizumab, a recombinant humanized mAb against IgE, for allergy, asthma and urticaria...