Lactococcus lactis as a vehicle for biotechnological production of proteins and clinical delivery of therapeutics
The Sarkar Lab has genetically engineered the Gram-positive bacteria Lactococcus lactis to secrete a single-chain insulin analog (SCI-57) that is bioactive at gut physiological pH, demonstrating the first functional expression of an insulin analog in this bacteria.
L. lactis, widely used in fermented food production, can be employed as an in vivo drug delivery system. This system is applicable to oral insulin delivery, where the traditional need for two-chain synthesis, protein purification, and temperature-sensitive storage can be bypassed with this technology. An oral delivery route is non-invasive compared to the current standard of diabetes treatment and results in higher bioavailability because of reduced enzymatic degradation. The researchers demonstrated that the induction time prior to the introduction of nisin for gene transcription is important for the growth of L. lactis. Optimization of the signal peptide Usp45sp will allow the secretion potential of L. lactis to be further exploited.
- Lactococcus lactis safe for human consumption
- Deliver higher effective dosage of drug as survives passage through intestine
- Eliminate need for purification and two-chain synthesis of insulin
- Greatly reduce cost of insulin development
- Attenuate proteolytic degradation
- In vivo drug delivery system
- Enhance protein secretion in bacterial hosts
Schematic representation of SCI-57 construct engineered in L. lactis
Stage of Development:
In vitro testing