In Utero Molecular-Targeted Drug Therapies: Translational Principles, Pharmacologic Considerations, and Emerging Clinical Applications

Advances in fetal diagnosis and molecular medicine have opened new opportunities for in utero molecular-targeted drug therapy, shifting fetal treatment from purely procedural interventions toward pharmacologic strategies that address disease mechanisms before irreversible organ damage occurs. In this review, we highlight recent advances in in utero drug therapy, focusing on molecular-targeted approaches with emerging clinical or trial-level evidence. Early clinical experience and ongoing trials have demonstrated the feasibility of achieving therapeutically relevant fetal drug exposure, although the strength of evidence varies considerably across therapeutic classes. However, significant challenges remain, including optimization of fetal drug delivery, characterization of fetal pharmacokinetics and pharmacodynamics, long-term safety assessment, and ethical considerations. The current evidence base ranges from single case reports to ongoing Phase 3 clinical trials, underscoring both the promise of prenatal molecular therapeutics and the need for further prospective evaluation. Continued integration of fetal imaging, genomics, ethics and pharmacology will be essential to advance safe and effective prenatal precision therapies.