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Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

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Perspective

Molecular Fingerprinting by Single Cell Clone Analysis in Adverse Drug Reaction (ADR) Assessment

Author(s): Anjan K. Banerjee *

Volume 17, Issue 1, 2022

Published on: 27 July, 2021

Page: [1 - 6] Pages: 6

DOI: 10.2174/1574886316666210727150415

Abstract

Causality assessment for idiosyncratic ADRs mainly relies on epidemiology, signal detection and less often on proven or plausible mechanistic evidence of the drug at a cellular or organ level. Distinct clones of cells can exist within organs of individual patients, some conferring susceptibility to well-recognised Adverse Drug Reactions (ADRs). Recent advances in molecular biology have allowed the development of single-cell clonal techniques, including single-cell RNA sequencing (scRNA-seq) to molecularly fingerprint ADRs and distinguish between distinct clones of cells within organs in individuals, which may confer differing susceptibilities to ADRs. ScRNA- seq permits molecular fingerprinting of some serious ADRs, mainly in the skin, through the identification of Directly Expressed Genes (DEG) of interest within specific clones. Overexpressed DEGs provide an opportunity for targeted treatment strategies to be developed. scRN A-seq could be applied to a number of other ADRs involving tissues that can be biopsied/sampled (including skin, liver, kidney, blood, stem cells) as well as providing a molecular basis for rapid screening of potential therapeutic candidates, which may not otherwise be predictable from a class of toxicity/organ involvement. A framework for putative assessment for ADRs using scRNA-seq is proposed as well as speculating on potential regulatory implications for pharmacovigilance and drug development. Molecular fingerprinting of ADRs using scRNA-seq may allow better targeting for enhanced pharmacovigilance and risk minimisation measures for medicines with appropriate benefit-risk profiles, although cost-effectiveness and other factors, such as frequency/severity of individual ADRs and population differences, will still be relevant.

Keywords: Adverse drug reactions (ADRs), directly expressed genes, RNA sequencing, epidemiology, fingerprinting, single cell clone.

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Graphical Abstract

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