Peptide-based nanoparticles for extrahepatic delivery of therapeutic RNA

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INTRODUCTION
The field of RNA therapeutics has significantly evolved since the first FDA approval of an RNA-based drug in 1998. Fomivirsen, now withdrawn, is an antisense oligonucleotide administered through intravitreal injections for treating cytomegalovirus retinitis in patients with a compromised immune system. With eighteen RNA medicines approved by the FDA and/or EMA, including one aptamer, nine antisense oligonucleotides, five short interfering RNAs (siRNAs), and two messenger RNAs (mRNAs) (Table 1), RNAs are on their way to becoming mainstream drugs. However, the application of RNA therapeutics is still restricted to a few disease areas: liver regulation of gene expression, a limited number of rare genetic diseases, and vaccines.