- For non-viral gene delivery system
There are various strategies developed non-viral vector system for endosomal escape.
- The ‘proton sponge' hypothesis: ‘Proton sponge' effect has been seen in some cationic polymers which contain protonable amine groups with pKa close to endosomal/lysosomal pH can be used for gene delivery During acidification of endosomes the cationic polymers become protonated so that the H+ influx is increased and thereby Cl- concentration is increased inside the endosome leading to water influx. As a result the endosome swells and eventually ruptures.
- Flip - Flop mechanism: Due to electrostatic interaction of cationic lipoplexes and anionic lipids of endosomes facing towards cytoplasm there is lateral diffusion of lipids resulting in displacement of nucleic acids from lipoplexes to cytoplasm.
- Pore formation: In a peptide based gene delivery system a peptide named GALA which can undergo conformation change at low pH forms a pore in the vesicular membrane when incorporated.
- Photochemical internalizaton: This technique uses photosensitizers which can bind to and localize in the plasma membrane. These photosensitizers become confined to endosomal membrane during endocytosis and remain inactive. When irradiated with light of a particular wavelength they produce reactive oxygen species resulting in lysis of endosomes.
8-1.9 Advantages of Gene Therapy
- The ‘proton sponge' hypothesis: ‘Proton sponge' effect has been seen in some cationic polymers which contain protonable amine groups with pKa close to endosomal/lysosomal pH can be used for gene delivery During acidification of endosomes the cationic polymers become protonated so that the H+ influx is increased and thereby Cl- concentration is increased inside the endosome leading to water influx. As a result the endosome swells and eventually ruptures.
- Gene therapy can cure genetic diseases by addition of gene or by removal of gene or by replacing a mutated gene with corrected gene.
- Gene therapy can be used for cancer treatment to kill the cancerous cells.
- Gene expression can be controlled.
- Therapeutic protein is continuously produced inside the body which also reduces the cost of treatment in long term.