Chimeric Construct Engineering with Human Variant HLA-A^*02:01:01:01

The containment of lethal acute lung injuries, acute respiratory distress syndrome (ARDS) and cytokine storm arising from severe interstitial pathology, including COVID-19, requires an efficient design and therapeutic implementation of new drugs and biomedical technologies. This demand calls for adequate biomodels in preclinical research and trial. Genetic variations between ethnic groups condition the specific mechanisms of drug efficiency. Modelling this population-specific genetic polymorphism allows a comprehensive research into the molecular bases of pharmacological action, also in immune biology. The engineered chimeric molecule encodes a MHC class I product that combines human ß₂-microglobulin, the α1 and α2 domains of Russian ethnic allelic variant HLA-A*02:01:01:01 and murine H2-K complex α3 domain. The linear chimeric gene fragment will be used to obtain humanised lineages of transgenic mice.

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