The final destination of the cargo for RNA interference is the cytosol214. However, gene editing requires access to DNA. Strategies for nuclear targeting generally fall into two categories: using particles that are small enough to pass through the nuclear pore complex, or incorporating functionality that is used after endosomal escape214,279. NP properties can passively influence intracellular trafficking and the final destination179, but particles can also be actively targeted to specific intracellular sites and organelles, such as the mitochondria27. Defects within the mitochondrial DNA can also play a significant role in disease onset. However, success with mitochondrial DNA genetic engineering is currently limited to highly controlled in vitro settings214.
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