Technical Considerations of Pharmacokinetic Assays for LNP-mRNA Drug Products by RT-qPCR
Lipid nanoparticle-messenger RNA (LNP-mRNA) drug products are a growing class of drug modalities. The unique composition of these drug products requires multiple measurements to account for the different components of these drug modalities. Pharmacokinetic (PK) measurements include measurement of the encapsulated mRNA and components of the LNP in circulation to understand the effectiveness of the therapeutic mRNA. The PK measurements can utilize many different platforms including PCR. Current regulatory guidance documents for bioanalytical method validation are specific to ligand binding and chromatographic assay methods and difficult to interpret for use with molecular workflows. The purpose of this paper is to provide information on considerations for validation of regulated reverse transcription quantitative PCR (RT-qPCR) assays that are used to support the pharmacokinetic analysis of LNP-mRNA drug products.
Authors
- Kelly Colletti
- Mark Wissel
- Darshana Jani (ORCID: https://orcid.org/0000-0002-6329-7759)
- Susan Carr Zondlo
- Jason Pennucci (ORCID: https://orcid.org/0000-0002-7689-1896)
- Sanjay L. Dholakiya
- Jennifer N. Durham (ORCID: https://orcid.org/0000-0001-9097-9125)
- Wendy O. Adamowicz
- Johannes Stanta (ORCID: https://orcid.org/0000-0001-6015-515X)
- Lara Duchstein
- Bryan Gullick
- Bin Xu (ORCID: https://orcid.org/0000-0002-1294-4506)
- Jenny Valentine
- Mohamed Benhammadi (ORCID: https://orcid.org/0000-0002-1564-7734)
- Benjamin Moritz
- Mikael Kubista (ORCID: https://orcid.org/0000-0002-2940-352X)
- Jacqueline Murphy
- Hsing‐Yin Liu (ORCID: https://orcid.org/0000-0001-7662-6390)
- Niketa Jani
- Alice Park
- Timothy L. Lochmann (ORCID: https://orcid.org/0000-0002-3368-6067)
- Mitra Azadeh
- Amy Lavelle
- Mengfei Cheng
- Rajitha Doddareddy
- Swarna Suba Ramaswamy
- Kate Herr
- Marie-Soleil Piché
- Suresh Peddigari
- Sebastián Guelman
- Amanda Hays (ORCID: https://orcid.org/0000-0002-3429-4727)
- Yanchun Li (ORCID: https://orcid.org/0000-0003-1314-3812)
- Venkata R. Vepachedu (ORCID: https://orcid.org/0009-0000-6457-882X)
- Meizhen Wu (ORCID: https://orcid.org/0009-0001-7702-0080)
- Enric Bertran Portabella
- Geng Li (ORCID: https://orcid.org/0000-0002-2441-2427)
- Haiyan Ma
- A. Srinivas Reddy (ORCID: https://orcid.org/0000-0003-4212-1460)
- Kaarthik John
- Oskar Johansson
- Muriel Smet
- Katherine Veirs
Institutions
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Pennsylvania Department of Health (US)
- Johnson & Johnson (United States) (US)
- Charles River Laboratories (Netherlands) (NL)
- Eli Lilly (United States) (US)
- Northern Michigan University (US)
- Regeneron (United States) (US)
- Mary Lyon Centre at MRC Harwell (GB)
- 490 BioTech (United States) (US)
- Bristol-Myers Squibb (United States) (US)
- Research Complex at Harwell (GB)
- Czech Academy of Sciences, Institute of Biotechnology (CZ)
- Celerion (United States) (US)
- Ultragenyx Pharmaceutical (United States) (US)
- Moderna Therapeutics (United States) (US)
- Novartis (United States) (US)
- Sanofi (Belgium) (BE)
- Charles River Laboratories (United States) (US)
- American College of Clinical Pharmacy (US)
- Tataa Biocenter (Sweden) (SE)
- Thermo Fisher Scientific (United States) (US)
- Intralytix (United States) (US)
- Beam Therapeutics (United States) (US)
- Delaware Technical Community College (US)
Publication Details
- Journal
- The AAPS Journal
- Published
- 2025-09-18
- DOI
- https://doi.org/10.1208/s12248-025-01122-w
- Citations
- 2
- Primary Topic
- Molecular Biology Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 1.61