山大药剂基因治疗剂型开发资料.ppt

* Mechanisms of endosomolysis. (a) Pore formation. Pore forming peptides induce bending of the membrane and contiguity of the bilayer leaflets, thus opening a pore in the membrane and facilitating release of endosomal contents. (b) Flip-flop. The lipoplex becomes endocytosed (1), and destabilizes the membrane, inducing flipping of anionic lipids from the cytoplasm to face the endosomal lumen (2). The anionic lipids form charge neutral ion pairs with cationic lipids of the complex (3), thus displacing the DNA and releasing it into the cytoplasm (4). (c) Proton sponge. The polyplex exacerbates proton accumulation in the endosome (1), inducing passive chloride influx (2), and causing osmotic swelling and endosomal rupture (3). * Mechanisms of endosomolysis. (a) Pore formation. Pore forming peptides induce bending of the membrane and contiguity of the bilayer leaflets, thus opening a pore in the membrane and facilitating release of endosomal contents. (b) Flip-flop. The lipoplex becomes endocytosed (1), and destabilizes the membrane, inducing flipping of anionic lipids from the cytoplasm to face the endosomal lumen (2). The anionic lipids form charge neutral ion pairs with cationic lipids of the complex (3), thus displacing the DNA and releasing it into the cytoplasm (4). (c) Proton sponge. The polyplex exacerbates proton accumulation in the endosome (1), inducing passive chloride influx (2), and causing osmotic swelling and endosomal rupture (3). * Mechanisms of endosomolysis. (a) Pore formation. Pore forming peptides induce bending of the membrane and contiguity of the bilayer leaflets, thus opening a pore in the membrane and facilitating release of endosomal contents. (b) Flip-flop. The lipoplex becomes endocytosed (1), and destabilizes the membrane, inducing flipping of anionic lipids from the cytoplasm to face the endosomal lumen (2). The anionic lipids form charge neutral ion pairs with cationic lipids of the complex (3), thus displacing the DNA and releasing it i