RNA-SEQ based toxicogenomics comparison of airway cells exposed to Vype TM epen vapour and cigarette smoke.

Transcription

1 RNA-SEQ based toxicogenomics comparison of airway cells exposed to Vype TM epen vapour and cigarette smoke Emmanuel Minet, PhD CBTOX 2017, Goiânia

2 CONFLICT OF INTEREST STATEMENT I declare that this work was fully funded by British American Tobacco (Investments) Ltd and that myself and my co-workers were full time employees of British American Tobacco (Investments) Ltd for the duration of the research.

3 Agenda E-cigarettes & Vype e-pen 21 st Century toxicology In vitro RNA-seq toxicogenomics Conclusions and perspectives

4 Electronics and battery coil E-liquid E-cigarettes have evolved rapidly Vype epen Development of e-cigarettes

5 In the UK there is a growing consensus on e-cigarette harm reduction potential Kevin Fenton, Public Health Director of Health and Wellbeing: The wider body of evidence consistently finds that e-cigarettes are less harmful than smoking E-cigarettes: an evidence update The current best estimate is that e-cigarettes are around 95% less harmful than smoking Nicotine without smoke: tobacco harm reduction Promote e-cigarettes widely as substitute for smoking says new RCP report Electronic cigarettes (also known as vapourisers) Compared to tobacco products, electronic cigarettes are significantly safer

6 Assessment strategy for e-cigarettes 01 E M I S S I O N S E X P O S U R E R I S K Untargeted emissions Puffing behaviour Clinical BoBE E M I Targeted S S I O N S emissions E X P O S U R E R I S K Average daily Risk perception Untargeted Environmental emissions Puffing consumption behaviour Clinical Post market BoBEsurveillance emissions Targeted emissions Average Clinical PK daily Risk perception Environmental consumption Clinical BoE Post market surveillance emissions Clinical PK Clinical BoE Core elements in vitro reg of tox our in vitro assessment in vitro disease programme modelsfor e-cigarettes in vitro systems science in vitro reg tox in vitro disease models in vitro systems science 03 Murphy, JJ (2017). Pan European Networks, Government 21:52-55 and Murphy J et al (2017) Reg Tox Pharm (in press)

7 Systems biology: 21 st century toxicology In vitro relevant models, non-animal, human clinical Unbiased high density, high throughput, top down Mode of action

8 Experimental design: 3D primary cells aerosol exposure system MucilAir Exposure chamber Smoke engine RM20S Air Media

9 Experimental workflow for e-cigarette RNA-sequencing work Air 3R4F 1/30 E-cig 1/7 & 1/3 Air 3R4F 1/30 E-cig 1/7 & 1/3 Haswell et al., Sci Reports (2017)

10 Reduced biological impact of e-cigarette aerosol vs cigarette smoke RNA-seq DEGs Validation Correlation DEG 3R4F in two donors RNA-seq 3R4F vs air in 3 donors qpcr Haswell et al., Sci Reports (2017)

11 Functional enrichment analyses of e-cigarette aerosol and cigarette smoke Gene Fold Change scale (log) Haswell et al., Sci Reports (2017)

12 Mapping genes contributing to tobacco-related adverse events AOP: EGFR activation leading to decreased lung function Enrichment analysis tools against known disease mechanisms/events Luettich et al., App in vitro Tox (2017)

13 Our comprehensive peer-reviewed contribution on e-cigarette risk assessment

14 SUMMARY Scientific framework established to substantiate risk reduction potential of e-cigarettes In vitro toxicogenomics shows reduced effect of e-cigarette aerosols In vitro omics offer an unbiased coverage of the biological changes Limited impact of e-cigarette on global airway transcriptome Provided information on mechanism of action based on impacted pathways Changes can be matched against key disease events mapped in AOPs All data are being published in peer review literature

15 THANK YOU Andrew Baxter Anisha Banerjee Chris Proctor Clive Meredith David Azzopardi David Thorne Frazer Lowe Ivan Verrastro James Murphy Jason Adamson Linsey Haswell Oscar Camacho Sarah Corke Tomasz Jaunky Marianna Gaca British American Tobacco (Investments) Limited All rights reserved. No part of these materials may be reproduced in any form or by any means without the prior written consent of British American Tobacco (Investments) Limited and no responsibility or liability is accepted for any third party reliance on any data contained herein. The data and information used in these materials has been compiled from a number of sources.