SLAM-Dx | Diagnostic drug response-profiling using SLAMseq

Summary
One of the greatest challenges today is to select the right drug for the right patient at the right time. A lack of diagnostic tools for predicting therapy response currently hampers patient-tailored treatment decisions in the clinic with severe implications for economy and – most importantly – patient survival.

Profiling transcriptional responses to drug treatment is a key method for probing the activity of targeted therapeutics and guiding their use in the clinic. A major limitation of established gene expression profiling techniques (such as microarrays and RNA-seq) is their limited time resolution precluding the distinction of direct from secondary transcriptional responses to drug therapy. This hampers their utility for deciphering drug action and guiding patient-tailored treatment decisions.

To overcome this problem, as part of an ERC-StG project (Systematic in-vivo analysis of chromatin-associated targets in leukemia, 336860) I have co-developed thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAMseq) as a rapid, robust and highly scalable method for the unbiased quantification of changes in mRNA production upon cell perturbations. Its unique features (low input cell numbers, short treatment-to-sample time, 1-day protocol library preparation in 96-well format) may qualify SLAMseq as the first method to probe the function, efficacy and selectivity of candidate therapeutics in primary (tumor) cells with unprecedented precision and on a large scale.

In this ERC-PoC project, I propose to establish technical and commercial proof-of-concept for SLAMseq’s application in preclinical and clinical drug development and optimization, and for patient-tailored treatment selection. Upon the successful proof-of-concept for SLAMseq’s application as diagnostic tool, SLAM-Dx has the potential to revolutionize translational research and personalised medicine in a variety of disease areas.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/862507
Start date: 01-10-2019
End date: 31-03-2021
Total budget - Public funding: 150 000,00 Euro - 150 000,00 Euro
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Original description

One of the greatest challenges today is to select the right drug for the right patient at the right time. A lack of diagnostic tools for predicting therapy response currently hampers patient-tailored treatment decisions in the clinic with severe implications for economy and – most importantly – patient survival.

Profiling transcriptional responses to drug treatment is a key method for probing the activity of targeted therapeutics and guiding their use in the clinic. A major limitation of established gene expression profiling techniques (such as microarrays and RNA-seq) is their limited time resolution precluding the distinction of direct from secondary transcriptional responses to drug therapy. This hampers their utility for deciphering drug action and guiding patient-tailored treatment decisions.

To overcome this problem, as part of an ERC-StG project (Systematic in-vivo analysis of chromatin-associated targets in leukemia, 336860) I have co-developed thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAMseq) as a rapid, robust and highly scalable method for the unbiased quantification of changes in mRNA production upon cell perturbations. Its unique features (low input cell numbers, short treatment-to-sample time, 1-day protocol library preparation in 96-well format) may qualify SLAMseq as the first method to probe the function, efficacy and selectivity of candidate therapeutics in primary (tumor) cells with unprecedented precision and on a large scale.

In this ERC-PoC project, I propose to establish technical and commercial proof-of-concept for SLAMseq’s application in preclinical and clinical drug development and optimization, and for patient-tailored treatment selection. Upon the successful proof-of-concept for SLAMseq’s application as diagnostic tool, SLAM-Dx has the potential to revolutionize translational research and personalised medicine in a variety of disease areas.

Status

CLOSED

Call topic

ERC-2019-POC

Update Date

27-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.1. EXCELLENT SCIENCE - European Research Council (ERC)
ERC-2019
ERC-2019-PoC