Fig. 5

Possible methods of multiplexed shRNA-miRs delivery. A Ex vivo administration of therapeutics can be done on the patient's stem cells or T cell transplants. The cells are harvested from the patient’s tissue into a culture vessel, then subjected to transfection by using liposomes or nanoparticles; or transduction by using viral vectors such as adenoviral vectors or lentiviral vectors. Lentiviral vectors can integrate the therapeutic gene into the host genome. B Non-specific in vivo administration can utilize dendrimers, polymers, and liposomes to encapsulate the therapeutics. Various DsiRNA can also be added into the construct along with the CCR5 knockout siRNA. As the nanoparticles attach to cells, they can fuse with the cell membrane and release their content into the cell. C Therapeutics can be coupled with antibodies or aptamers to target specific cells. The therapeutics can latch to the cell receptor and enter the cell by receptor-ligand mediated endocytosis. D Envelope-type nanoparticles such as liposomes, dendrimers, and polymers can be enriched with targeting molecules to convey the siRNA to specific cells. The nanoparticles then can fuse with the cell membrane and deliver therapeutics while also preventing the siRNA degradation by ribonucleases