Synthetic biology associated with nanotechnology: obtaining transmembrane proteins for the production of biomimetic nanovesicles by microfluidic process

Abstract

Despite the large increase in diseases involving the central nervous system (CNS) in recent decades, drug availability is still low. The major limitation is the permeation of drugs through the blood-brain barrier (BBB) to reach the site of therapeutic action. A strategy to overcome the limitation of drug delivery through the BBB is the use of biomimetic vesicles, with potential for targeted action, combining transmembrane proteins with liposomes and aiming to increase their biospecificity, as well as to circumvent the immune system. Liposomes, self-assembled systems of specific lipids, mimic cell membranes and can be used to deliver drugs. However, conventional liposomes have a short circulation time in the bloodstream and do not have specific targeting. For its synthesis, microfluidics is a technology that allows the production of these nanoaggregates in a homogeneous and reproducible way. In this way, this project has an innovative character for coupling synthetic biology applied to yeasts for the production of human trans-membrane proteins responsible for adhesion in the BBB to be used in biomimetic vesicles. In this approach, genetic engineering techniques will obtain membrane proteins with the potential for interaction with BBB, using Saccharomyces cerevisiae or Pichia pastoris as expression chassis. These proteins will be incorporated into liposomes during the microfluidic route of production. The project will be carried out in collaboration between microfluidics (LaNBDA - Unicamp), synthetic biology (LaBS - Unicamp), and neurobiology (Unifesp) laboratories. This research is part of the thematic project "Development of brain-on-a-chip microplatforms for in vitro central nervous system modeling". This approach will allow the development of new carriers and the phenomenological understanding of the interaction of different proteins with the blood-brain barrier, which may contribute to the advancement of nanobiotechnology in producing biomimetic nanovesicles. (AU)