AsPac J. Mol. Biol. Biotechnol. 2018 Vol. 26 (1) : 1-10 Lactococcus lactis : LAB model organism for bacteria-mediated therapeutic strategies Hanis Faudzi a , Habibah Faroque a , Suet Lin Chia b,c , Raha Abdul Rahim a , Sarah Othman a* a Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia b Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia c Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia Received 20th April 2018/ Accepted 12th July 2018 Abstract. Lactococcus lactis is a well-characterized, food-grade lactic acid bacterium (LAB) with generally recognized as safe (GRAS) status. Better understanding of this bacterium at a molecular level has led to the development of unprecedented genetic tools that enable the expression of heterologous proteins. Subsequently, the ability of L. lactis to express and deliver these proteins to eukaryotic hosts presents a promising approach to achieve potent treatments for various diseases. Here, we have reviewed the characteristics of L. lactis and the expression systems established for this LAB model organism. We also described the experimental applications of L. lactis in disease therapy, especially its role as a vector in vaccination strategies. Keywords: bactofection, lactic acid bacteria, Lactococcus lactis, vaccine, vector INTRODUCTION 1. Background During the 90’s, lactic acid bacteria (LAB) started to become popular starter cultures for the production of dairy and fermented food (Konings, 2000). This is particularly due to their ability to produce lactic acid as a major end product of carbohydrate fermentation (Kandler, 1983). Owing to their long history of use in food production, LAB have been proven as safe for human consumption and were certified as generally recognized as safe (GRAS) organisms by the US Food and Drugs Administration (FDA) (Kolida and Gibson, 2011). Currently, 13 genera have been classified under the LAB group, which include Lactococcus, Lactobacillus, Streptococcus, Pediococcus, Paralactobacillus, Enterococcus, Carnobacterium, Lactosphaera, Leuconostoc, Oenococcus, * Author for correspondence: Dr. Siti Sarah Othman, Senior Lecturer, Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. Email - sarahothman@upm.edu.my Tetragenococcus, Weisella, and Vagococcus (Stiles and Holzapfel, 1997). To date, efforts have been made to achieve a better understanding of LAB and to advance their application in health and nutrition. Improved knowledge of LAB has contributed to the development of heterologous protein expression systems, coupled with gene transfer mechanisms that have led to the employment of LAB as delivery agents for the treatment of diseases. Among them, Lactococcus lactis is the most- characterized LAB organism which has been extensively studied for biomedical applications. In this review, we discuss the properties of L. lactis, which made it an excellent LAB model. We also describe several L. lactis-based expression and delivery systems available, as well as a summary