Table 2.

Similarities and Differences Between Oligonucleotide Therapeutics and Existing Drugs

	Chemically synthesized drugs	Oligonucleotide therapeutics	Biopharmaceuticals
Molecular weight	Generally <1 kDa	Generally ≤10 kDa	Generally >30 kDa
Production method	Chemical synthesis	Chemical synthesis	Biotechnology
Target	Intracellular and/or extracellular	Intracellular and/or extracellular	Extracellular
Species specificity	Nonspecific	Occasionally species specific	Species specific
Metabolism/degradation	Activation or inactivation by metabolism	Degradation to nucleic acids and metabolism	In vivo degradation to amino acids
Predictability of toxicity	Unpredictable	On-target effects, predictable; off-target effects, unpredictable	Predictable
Toxicological mode of action	Off-target effects, (toxicity related to metabolites and nonspecific toxicity independent of mechanism of action)	Exaggerated pharmacology and off-target effects (target dependent/target independent)	Exaggerated pharmacology (known mechanism of action)