Fig. 1. Overview of strategies to increase protein production.

Currently, several strategies are approved or in development to increase protein production. a, In protein-replacement therapy, recombinant proteins are administered to replace a mutant variant or to supplement for a deficient variant in a patient. b, For gene therapy, viral vectors are used to deliver cDNA encoding functional proteins. c, For gene editing, specific mutations are corrected in situ by targeted DNA-editing or RNA-editing constructs (for example, transcription activator-like effector nucleases, zinc finger nucleases, CRISPR–Cas, base editors). d, For mRNA delivery, functional mRNA is delivered to cells to increase protein levels using various delivery modalities such as lipid nanoparticles (LNPs). e, RNA-targeted approaches include nucleic acid-based therapeutic (NBT) and small-molecule strategies. NBTs, such as antisense oligonucleotides, natural antisense transcript-specific oligonucleotides (AntagoNATs), small activating RNAs and microRNA blockers (antagomirs), modulate non-coding RNA-mediated regulation of transcription and translation through various mechanisms involving, for example, RNAse H, RNA-induced silencing complex-mediated RNA interference and steric blocking. Small molecules directly target RNA–protein interactions or recruit endogenous enzymes to target RNA, leading to protein upregulation.