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Experimental data demonstrate that GATA-3-specific DNAzymes do not lead to unspecific immune cell activation

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  • Results support favourable safety profile observed in toxicological studies and in recently completed first clinical trial of SB010

Marburg, Germany, 27 March 2012 – A paper published in Nucleic Acid Therapeutics (Dicke et al., 2012) found that the DNAzyme used in sterna biologicals’ drug candidate SB010, a novel inhaled GATA-3 antagonist for the treatment of moderate to severe Th2-driven asthma, does not lead to unspecific immune cell activation.

The researchers employed TLR-9-transfected HEK293 cells, macrophage cell lines and primary innate immune cells to establish whether the DNAzyme and especially the CpG motif of its catalytic domain leads to off-target effects. The unmethylated CpG motif is recognised by TLR-9 which can activate the innate immune system via NFκB. Furthermore, putative effects of the GATA-3-specific DNAzyme on the activation of neutrophil granulocytes and degranulation of mast cells/basophils were assessed.

No TLR-9 mediated or TLR-9 independent cell-stimulating activities of the DNAzyme were observed in any of the systems, further supporting the therapeutic potential of GATA-3- specific DNAzymes as previously reported (Sel et al., 2008).

References

Dicke T, Pali-Schöll I, Kaufmann A, Bauer S, Renz H, Garn H. Absence of Unspecific Innate Immune Cell Activation by GATA-3-Specific DNAzymes. Nucleic Acid Ther 2012. [Epub ahead of print]

Sel S, Wegmann M, Dicke T, Sel S, Henke W, Yildirim AO, Renz H. and Garn H. Effective Prevention and Therapy of Experimental Allergic Asthma Using a GATA-3-specific DNAzyme. J Allergy Clin Immunol 2008 (121): 910-916.

 

About SB010

sterna biologicals’ drug candidate SB010 is an inhaled DNAzyme-based GATA-3 antagonist. GATA-3 is the master transcription factor in regulating Th2-driven inflammatory diseases such as asthma. It is generally accepted that GATA-3 is necessary and sufficient for the production of key cytokines interleukin (IL)-4, IL- 5, and IL-13, which cause inflammation. In pre-clinical development, SB010 significantly reduced expression of these cytokines and was safe and well-tolerated in toxicological studies with negligible side-effects. DNAzymes are single-stranded DNA molecules comprising a catalytic domain flanked by two binding domains. The binding domains attach to a specific sequence of targeted mRNA (antisense), in case of SB010 GATA-3 mRNA. After binding to the target, the catalytic domain then cleaves the mRNA, thereby inhibiting relevant cytokine expression.

About asthma

Asthma is a major chronic inflammatory disease of the airways affecting an estimated 300 million people worldwide. In OECD countries, prevalence is around 10% and increasing, with greater than average prevalence amongst women, children, and the elderly.

About sterna biologicals
sterna biologicals GmbH & Co. KG, a spin-off from Marburg University (Germany), is an innovative biopharmaceutical company developing novel treatments for chronic inflammatory diseases of lung and skin such as asthma, atopic dermatitis, psoriasis, and COPD. By targeting transcription factors that play a pivotal role in regulating underlying inflammatory mechanisms, the company’s next generation antisense molecules (DNAzymes) already intervene at a very early stage in the disease formation process.

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sterna biologicals GmbH & Co. KG
Biomedizinisches Forschungszentrum (BMFZ) Hans-Meerwein-Straße 2
35043 Marburg
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