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In efforts to leverage biological time during drug development, Penn researchers investigated how gene expression in mouse organs changes over time and discovered that ~50% of protein-coding genome is expressed in a circadian clock dependent manner. Importantly, the majority of best-selling drugs and World Health Organization essential medicines directly target clock-regulated gene products. Since many of these drugs have short half-lives, they could greatly benefit from temporal dosing.
This information can be used to developing delayed-release formulations of therapeutics so that the time of release coincides with the highest expression of the drug target or transporter. The converse is also possible, timing a drug to avoid its rapid metabolism. This chronotherapy could be used to reduce off-target as well as adverse effects while increasing on-target efficacy. This invention applies to many drugs, diseases, and health conditions.