vtt csma technology

7/31/2019 VTT CSMA Technology

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High density RNAi screening withCell Spot Microarrays (CSMA)

VTT Technical Research Centre of Finland


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Cell Spot Microarrays (CSMA)

Discovery and validation of drug targets with highly miniaturized platform for cell-based RNAi screening

Genome-wide ultra HT RNAi screening (28.000 siRNA species in a single microtiter plate)

Rapid testing of subgenomic RNAi sets according to customers interests (e.g. kinases andphosphatases, GPCRs, druggable genome, epigenetic regulators)

High-content screening for multiparametric phenotypes designed according to the customers needs

Can replace conventional 384-well plate-based screens

Proprietary technology developed by VTT


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Applications of CSMA

A functional genomics tool for drug discovery and development with applications in

Drug target discovery and validation in high-content with multiple parameters

Compound screening (miniaturization enables screening also when the amount of

compound or other reagents is limited) Testing of the gene/drug sensitization effect in ultra HT manner

Modulation of drug efficacy by siRNA-mediated synthetic lethal gene-knockdowns

Mechanism-of-action studies

CSMA is validated with over 90 different cell lines (Rantala et al. BMC Genomics 2011, 12:162)


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Moreinformation

Reliable andreproducible

Rapid and cost-effective

Very fast

results

Less cellsneeded

Multiparametric phenotype analysis

Long term cell culture possible

All samples with up to 28.000 siRNAs are analyzed in a singlechip -> No interassay variability

Miniaturization enables HTS also when cells or other material(e.g. compounds) are limited

Fully compatible with microarray scanners -> Readout forgenome-scale screen with four markers in Compatible with rare cell types e.g.primary or patient-derived cells

Benefits of using Cell Spot Microarray


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Ultra-high-throughput assays

Samples from 120 x 384-well plates with robotically made siRNA transfection mixtures

46.000 transfections with spots150m in diameter and 375m spacing in single plate

1. siRNA molecules as spotted as microarrays

2. Cells are added on top

3. Cells adhere on spots and take up siRNA

4. In each spot one gene of the genome is silenced individually

5. Multiparametric assays for gene silencing effects

Principle of CSMA


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A cell spot microarray method for production of highdensity siRNA transfection microarrays.Rantala JK, Mkel R, Aaltola AR, Laasola P, Mpindi JP,Nees M, Saviranta P, Kallioniemi O.BMC Genomics. 2011 Mar 28;12:162.

A functional genetic screen reveals new regulators of 1-

integrin activity.

Pellinen T, Rantala JK, Arjonen A, Mpindi JP, Kallioniemi O,Ivaska J.J Cell Sci. 2012 Feb 1;125(Pt 3):649-61.

Systematic knockdown of epigenetic enzymes identifies anovel histone demethylase PHF8 overexpressed in

prostate cancer with an impact on cell proliferation,migration and invasion.Bjrkman M, Ostling P, Hrm V, Virtanen J, Mpindi JP,Rantala J, Mirtti T, Vesterinen T, Lundin M, Sankila A,

RannikkoA, Kaivanto E, Kohonen P, Kallioniemi O, Nees M.Oncogene. 2011 Nov 28. doi: 10.1038/onc.2011.512.

.

Published research using CMSA technology

SHARPIN is an endogenous inhibitor of 1-integrinactivation.Rantala JK, Pouwels J, PellinenT, Veltel S, Laasola P,Mattila E, Potter CS, Duffy T, Sundberg JP, Kallioniemi O,Askari JA, Humphries MJ, Parsons M, Salmi M, Ivaska J.Nature Cell Biol. 2011 Sep 25;13(11):1315-24. doi:10.1038/ncb2340

Integrative functional genomics analysis of sustainedpolyploidy phenotypes in breast cancer cells identifies anoncogenic profile for GINS2.Rantala JK, Edgren H, Lehtinen L, Wolf M, Kleivi K, Vollan HK,AaltolaAR, Laasola P, Kilpinen S, Saviranta P, Iljin K, KallioniemiO.Neoplasia. 2010 Nov;12(11):877-88.

Epigenetics of prostate cancer and the prospect ofidentification of novel drug targets by RNAi screening of

epigenetic enzymes.Bjrkman M, Rantala J, Nees M, Kallioniemi O.Epigenomics. 2010 Oct;2(5):683-9.


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Added value for the customer

VTT provides phenotypic analyses according tocustomers interests including in-houserecombinant antibody development possibility fornovel antigens.

VTT's customer-tailored projects cover also other

VTT technologies which can easily be combinedto larger entities.

The scientists at VTT performing the CSMAanalyses have a wide understanding of thebiology behind the obtained screening data.

We will perform a full bio-informatics analysis

and scientific interpretation of the obtainedresults as agreed with the customer, instead ofproviding raw screening data.


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Contacts and additional information

For further information, please contact:

Sampo SammalistoPh.D., Key Account ManagerVTT, Drug development and diagnostics

P.O. Box 1000 (Tietotie 2), FI-02044 VTT, FinlandTel. +358 20 722 [email protected]

Additional information:

www.vtt.fi/HealthBiotech

www.youtube.com/user/VTTFinland


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