Vector Development Timeline for Mucosal Vaccination and Treatment of Disease Using Lactococcus lactis and Design Approaches of Next Generation Food Grade Plasmids

Lactococcus lactis has been used historically in fermentation and food preservation processes as it is considered safe for human consumption (GRAS-Generally Recognized As Safe). Nowadays, in addition to its wide use in the food industry, L. lactis has been used as a bioreactor for the production of molecules of medical interest, as well as vectors for DNA delivery. These applications are possible due to the development of promising genetic tools over the past few decades, such as gene expression, protein targeting systems, and vaccine plasmids. Thus, this review presents some of these genetic tools and their evolution, which allow us to envision new biotechnological and therapeutic uses of L. lactis. Constitutive and inductive expression systems will be discussed, many of which have been used successfully for heterologous production of different proteins, tested on animal models. In addition, advances in the construction of new plasmids to be used as potential DNA vaccines, delivered by this microorganism, will also be viewed. Finally, we will focus on the scene of gene expression systems known as "food-grade systems" based on inducing compounds and safe selection markers, which eliminate the need for the use of compounds harmful to humans or animal health and potential future prospects for their applications.