CALIXAR has developed an innovative detergent/surfactant based approach consisting on native isolation and stabilization of therapeutic membrane protein targets such as GPCRs, ion channels, transporters. Here we will explain how this approach can stabilize membrane proteins by modifying their chemical environment instead of their native sequence. We will illustrate using case studies on targets of high medical relevance produced in their most native state without any single mutation, truncation or fusion and that were solubilized, affinity purified while maintaining their functional and structural integrities. A recent collaboration was initiated with Thermo Fisher Scientific as the world leader on the expression of difficult to express proteins. This collaborative effort we will help us tackle the production and characterization of very challenging but very promising and highly druggable targets such as GPCRs, ion channels & transporters. This native isolation approach represents a new hope for the development of more accurate drug discovery (SBDD, FBDD, Antibody discovery & vaccine) and provide a serious alternative to classical protein engineering approaches.