Combination therapy using nucleic acids and radio therapy
View Patent ↗The present invention relates to methods for increasing the efficiency of transformation of cycling cells, the methods comprising synchronizing cells at a first stage of the cell cycle, and transforming the cells at a second stage of the cell cycle within about one cell cycle of the first stage with a genetically engineered nucleic acid that encodes a desired gene product. The invention further relates to cancer therapy and, in particular, to methods of efficiently transforming cancer cells with nucleic acids that encode gene products that inhibit the growth of cancer cells.
1. A method of increasing the efficiency of transfection of cycling cells sensitive to electromagnetic radiation, comprising:
synchronizing said cells by contacting said cells with electromagnetic radiation, wherein said electromagnetic radiation is a member selected from the group consisting of: Gamma rays, X-rays, and ultraviolet rays, and
transfecting said cells within about one cell cycle with a nucleic acid that encodes a desired gene product,
wherein said efficiency of transfection is increased over cells not contacted with said electromagnetic radiation.
2. A method of claim 1 wherein said electromagnetic radiation synchronizes cells at a stage of the cell cycle when the nuclear membrane is substantially degraded.
3. A method of claim 1 wherein said electromagnetic radiation synchronizes cells at late S phase.
4. A method of claim 1 wherein said electromagnetic radiation synchronizes cells at the G2/M phase boundary.
5. A method of claim 1 wherein said electromagnetic radiation synchronizes cells at a stage other than a stage selected from the group consisting of: M phase, the late S phase, and the G2/M phase boundary.
6. A method of claim 1 wherein said gene product is foreign to said cells.
7. A method of claim 1 wherein said gene product is toxic to said cells.
8. A method of claim 7 wherein said gene product induces apoptosis.
9. A method of claim 1 wherein said nucleic acid is fully encapsulated in a lipid-nucleic acid particle.
10. The method of claim 1 , wherein said electromagnetic radiation is X-rays.
11. The method of claim 1 , wherein said cells are present within a mammal.