title: Quantification of therapeutic miRNA mimics in whole blood from nonhuman primates.
abstract: MRX34, a microRNA (miRNA)-based therapy for cancer, has recently entered clinical trials as the first clinical candidate in its class. It is a liposomal nanoparticle loaded with a synthetic mimic of the tumor suppressor miRNA miR-34a as the active pharmaceutical ingredient. To understand the pharmacokinetic properties of the drug and to rationalize an optimal dosing regimen in the clinic, a method is needed to quantitatively detect the miRNA mimic. Here, we report the development and qualification of a quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay in support of pharmacokinetic and toxicokinetic assessments in the nonhuman primate. Detection and quantification were performed on total ribonucleic acid (RNA) isolated from whole blood. The qualified range of the standard curve spans 6 orders of magnitude from 2.5 × 10(-7) to 2.5 × 10(-1) ng per reverse transcription (RT) reaction, corresponding to an estimated blood concentration from 6.2 × 10(-5) to 6.2 × 10(1) ng/mL. Our results demonstrate that endogenous as well as the exogenous miR-34a can be accurately and precisely quantified. The assay was used to establish the pharmacokinetic profile of MRX34, showing a favorable residence time and exposure of the miRNA mimic in whole blood from nonhuman primates.
authors.affiliation: Mirna Therapeutics, Inc., 2150 Woodward Street, Suite 100, Austin, Texas 78701, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kelnar
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Peltier
authors.forename: Neil
authors.initials: N
authors.lastname: Leatherbury
authors.forename: Jay
authors.initials: J
authors.lastname: Stoudemire
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Bader
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000032:analysis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002138:Calibration; D004355:Drug Stability; D004356:Drug Storage; D005615:Freezing; D057230:Limit of Detection; D008252:Macaca fascicularis / Q000097:blood*; D035683:MicroRNAs / Q000097:blood* / Q000627:therapeutic use
chemical_list: D035683:MicroRNAs