Systems and Methods for Diminishing Cell Growth and Inducing Selective Killing of Target Cells

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 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.

主权项

1. A biological system for diminishing cell growth or inducing selective killing of target cells, in particular pathogenic bacterial or fungal cells, or cancer cells, comprising 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, 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.