Bacterial vector
View Patent ↗The present invention relates to a combination of compounds for introducing nucleic acids and/or protein into animal cells, tissue, organs or organisms in vitro, extracorporal, or in vivo. This combination comprises preparations suitable for administration to an animal or human for medical purposes, comprising as one component a bacterial vector genetically manipulated to contain nucleic acid sequences comprising a transgene, and a second component for the subsequent transcription, possibly translation of the transgene by controlled induction of bacterial vector as it is present within the animal or human.
1. A method of administering a system of pharmaceuticals comprising:
administration to an animal or a human patient of a bacterial vector, the bacterial vector being a recombinant non-invasive or invasive bacterium which has been genetically modified to contain a transgene functionally linked to a saccharide inducible promoter, and
subsequent administration of an inductor saccharide to the patient that has previously received the bacterial vector.
2. The method of claim 1 wherein the bacterial vector is administered in a way selected from the group consisting of systemically, nasally, orally, rectally or otherwise mucosally.
3. The method of claim 1 wherein the saccharide inductor is administered independently from the localization that the bacterial vector has reached.
4. The method of claim 1 wherein the bacterial vector is based on bacteria selected from the group consisting of attenuated bacteria which are invasive to animal cells and bacteria commensal to animal cells or to animals.
5. The method of claim 1 wherein the saccharide inducible promoter and the inductor saccharide are selected from combinations consisting of the arabinose promoter and L-arabinose, the rhamnose promoter and rhamnose, and the xylulose promoter and xylulose.
6. The method of claim 1 wherein the saccharide inducible promoter is the regulatory module of a bacterial L-arabinose operon.
7. The method of claim 6 wherein the bacterial L-arabinose operon originates from E. coli.
8. The method of claim 1 wherein the transgene encodes a structural protein or a reactive RNA species.
9. The method of claim 1 wherein the transgene encodes synthetic pathway enzymes for the synthesis of biologically or pharmaceutically active effector molecules.
10. The method of claim 1 wherein the transgene encodes a peptide catalyzing the conversion of a pro-drug to a drug.
11. The method of claim 1 wherein the transgene encodes the product of a suicide gene.
12. The method of claim 11 wherein the suicide gene is selected from the group consisting of bacteriotoxic and bacteriolytic genes.
13. The method of claim 1 wherein the bacterial vector is genetically manipulated to express a heterologous inductor saccharide transporter system or a mutant inductor saccharide transporter system.
14. The method of claim 1 wherein the bacterial vector is genetically manipulated to express its intrinsic inductor saccharide transporter system at increased levels.
15. The method of claim 1 wherein the bacterial vector is genetically manipulated by inactivation of the metabolic pathway of the inductor saccharide.
16. The method of claim 1 wherein the bacterial vector is genetically manipulated to contain a heterologous secretion system.
17. The method of claim 1 wherein the transgene encodes a signal sequence of a secretion system.
18. The method of claim 1 wherein the medical treatment is administration of a vaccine.
19. The method of claim 1 wherein the medical treatment is treatment for tumors.
20. The method of claim 1 wherein the medical treatment is treatment for probiotics or functional food.
21. The method of claim 1 wherein the inductor saccharide is a saccharide analogon.
22. The method of claim 1 wherein the transgene comprises a coding sequence selected from the group consisting of sequences encoding synthetic pathway enzymes for the production of an immunomodulating compound or a toxic compound, or sequences encoding an antibody, a heterologous peptide, or a self-antigen.
23. The method of claim 1 wherein the transgene comprises a monitoring transgene.
24. The method of claim 23 wherein the medical treatment is monitoring of tumor tissue by spectroscopy or luminometric analysis.