Challenges identifying efficacious miRNA therapeutics for cancer

Figures & data

Table 1. Delivery vehicles for oligonucleotides.

Delivery vehicle	Specificity	Advantages	Disadvantages
Liposomes	Form lipoplexes by electrostatically interaction of a mixture of cationic lipids with polyanionic nucleic acids.	Biocompatible Biodegradable Reduction of toxicity [16]	Limited storage conditions Short half life Low stability [16]
Polymers	Use of cationic (PEI) or neutral (PLGA) polymers. Highly efficient encapsulation and a net cationic charge promise tolerable interactions with anionic miRNAs. Neutral polymer needs to be coated with cationic reagent for efficient delivery.	Natural polymers: Biocompatible Biodegradable Less toxic Synthetic polymers: Biocompatible [17]	Natural polymers: Structurally more complex Extraction process is complicated. Synthetic polymers: Toxic Non-degradable [17]
Conjugates	Conjugation of lipids or receptor-binding molecules (e.g. aptamers) directly to the nucleic acid.	Selective targeting Intracellular delivery High stability Less toxic [18]	Aggregation Endosomal entrapment [18]
Exosomes	Exosomes used to deliver RNA or pharmaceutically active substances. Exosomes are small and naturally existing in humans, they are able to fuse with the cell membrane and avoid the endosome.	Naturally present in body fluids Immunocompatible Low toxicity Able to cross the blood brain barrier [23]	Rapid clearance from blood Low drug loading Largely uncharacterized complexity [23]
Viral	Lentiviruses, adenoviruses and adeno-associated viruses (AAVs) can be used to deliver miRNAs into the cells by efficiently expressing miRNA genes.	High transfection efficiency Low toxicity [20]	Low packaging capacity High production cost Antigenicity [20]

Figure 1. Modification of nucleic acids. O-MOE is O-(2-Methoxyethyl); OMe is O-Methyl; LNA is locked nucleic acid; F is Fluoro.

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