Engineered Lactococcus Lactis for the controlled production of KGF
The present invention relates to a genetically modified probiotic microorganism expressing the human keratinocyte growth factor (KGF / FGF7). Vaginal atrophy, caused by the reduction of circulating estrogens, can be treated with KGF (keratinocyte growth factor) which, administered locally, restores vaginal trophism without systemic effects.
The invention is based on the engineering of a lactobacillus compatible with the vaginal microenvironment to inducibly produce KGF. The procedure used concerns the amplification of the KGF gene from human fibroblasts. To obtain the release of KGF by lactobacillus cells, a construct was generated, containing a signal sequence for the secretion, which was transferred to the bacterial strain under an inducible expression system, to allow the production of the KGF protein to be controlled. The efficacy of the KGF produced by the engineered microorganism was tested in human vaginal cells. In the known technique, oral hormone replacement therapy (HRT) is used, which however is not recommended both in women previously suffering from oncological pathologies and in healthy women, as it is correlated to a higher incidence of cancer.
- Treatment of conditions of vaginal atrophy, dysuria, vaginal pain and / or vaginal dryness induced by a postmenopausal state, by surgery, by a pathology and / or by chemotherapy or radiotherapy treatments.
- Safe, used as a drug;
- Controlled release by exogenous administration of a food supplement;
- The release occurs directly in the affected tissues, eliminating the risks of systemic exposure and allowing greater efficacy and tolerability of the treatment.