Synthetic Delivery Systems for Intravenous Administration of Nucleic Acids

At present, there are no intravenously administered nucleic acid-based therapeutics that have been approved for human use. This reflects the difficulties in applying nucleic acid-based drugs: they are nuclease sensitive and have difficulties in reaching their site of action. Important challenges for intravenously administered nucleic acid formulations are the requirements that they can transport the nucleic acids efficiently in the circulation, have the ability to direct nucleic acids to the desired cell type and are able to steer their intracellular processing. Here, we evaluate nanotechnological strategies that improve the pharmacokinetics and colloidal stability of nucleic acids in the bloodstream, focus biodistribution towards the target tissue and facilitate interactions with and trafficking within the desired cell type.