| 摘要 |
The invention relates to a biological system for diminishing cell growth or inducing selective killing of target cells, in particular pathogenic bacterial or fungal cells, or cancer cells. The biological system according to the invention is based on toxin-antitoxin systems, as found in prokaryotic plasmids and their host chromosomes. The biological system comprises a vehicle with a first nucleic acid sequence or amino acid sequence encoding for a prokaryotic toxin of a prokaryotic toxin-antitoxin pair, and a second nucleic acid sequence or amino acid sequence encoding for the corresponding prokaryotic antitoxin of the prokaryotic toxin-antitoxin pair. The system is characterized in that the toxin and/or the antitoxin is operably linked to a protein output modifier (POM) that comprises a nucleic acid sequence or amino acid sequence that modifies the relative rate of transcription, mRNA stability, mRNA translatability or protein stability of the toxin and/or antitoxin thereby changing the relative ratio in the concentration of the toxin and/or the antitoxin within the target cells and/or, where applicable, within non-target cells by either decreasing the antitoxin outputs in the target cells (killing) and/or increasing the antitoxin outputs in the non-target cells (protection) relative to the toxin outputs, and/or by increasing the toxin outputs in the target cells (killing) and/or decreasing the toxin outputs in the non-target cells (protection) relative to the antitoxin outputs. The invention also relates to a pharmacological composition to be used in the treatment of pathogenic diseases. The invention further relates to the use of the biological system for therapy of a pathological condition, diagnostics, theranosis, drug discovery, Screening, creating animal models, target molecule identification and validation. In a further aspect, the invention also relates to a drug delivery system for delivering a vehicle to target cells by means of biologically-derived nanocells (minicells). The invention also relates to a method for delivery of a substance to target cells |
