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Question

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Vector unpacking is generally assumed to be neces- sary for DNA release and gene expression, but the extent to which dissociation affects gene delivery is unclear For lipoplexes, it has been proposed that fusion of the cationic lipid with endosomal membrane lipids facili tates not only endosomal escape but also DNA release13. Polyplexes have been observed to localize intact to the nucleus, where they presumably undergo dissocia tion145. For certain polyplexes, mechanistic studies have reported slow vector unpacking as an explanation for decreased transfection efficiency16. Lipoplex-delivered plasmids are more efficiently expressed by nearly tenfold on the basis of protein expression per plasmid num ber in the nucleus - than polyplex-delivered plasmids, which might be a potential consequence of incomplete polyplex dissociation in the nucleus7.

Explanation / Answer

Particles or organisms entering the cell through endocytic pathway are trapped in endosomes. After which they are transferred to lysosomes which have active degradation enzymes. These enzymes degrade the particles and inactivate the particles or microorganisms. So to protect from the degradation, different viruses and bacteria have developed, evolved and adapted efficient mechanism of endosomal escape.

Reseach on understanding the endosomal escape mechanism has gained interest to develop new therapeutic targets and improving cellular delivery of therapeutics.

The different types of endosomal escape mechanisms include-

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