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While phosphorylation of proapoptotic NOXA and BAD promotes glucose consumption through PPP and glycolysis, respectively, the anti-apoptotic BCL-XL increases the efficiency of ATP synthesis by decreasing a proton leak within ATP synthase (137, 138)

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While the first approved oligonucleotide therapeutics were unconjugated strands delivered via formulations like lipid nanoparticles (LNPs), and small molecule-ON conjugates (e.g., GalNAc-siRNAs) have since reached the clinic, conjugation to larger targeting moieties offers a distinct strategy to overcome persistent challenges

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