Stages and barriers for delivery of nucleic acids to tumour cells. Delivery technologies for nucleic acids are designed to overcome several barriers dependent on the route of administration. For systemic administration, the delivery technology must protect the nucleic acid from clearance or degradation to permit extravasation and accumulation into the target tissue. It must then facilitate distribution through the tissue to the target cell type. Finally, the delivery technology must enable efficient intracellular delivery by crossing the cellular membrane and escaping endosomes, while avoiding endo-lysosomal trapping and expulsion from the cell by recycling. For nucleic acid modalities requiring access to the nucleus, there is the additional barrier of the nuclear membrane to overcome. ASO, antisense oligonucleotide; RISC, RNA-induced silencing complex; siRNA, short interfering RNA; miRNA, microRNA; mRNA, messenger RNA.