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DNA encircled bilayers (DEB) for the study of membrane proteins

Reference Number TO 24-00027

Challenge

Lipid bilayers and lipid-associated proteins play a crucial role in biology. As in vivo studies and manipulation are inherently difficult, several membrane-mimetic systems have been developed to enable investigation of lipidic phases, lipid-protein interactions, membrane protein function and membrane structure in vitro. However, stability, control of size and shape, or site-specific functionalization remains difficult to achieve with established membrane mimetics based on membrane scaffolding proteins (MSPs, e.g. Nanodisc ®), polymers or peptides.

ssDNA minicircles react with complementary strands carrying alkyl groups in red thus forming (a.) a double-stranded DNA minicircle. In the presence of lipids (b.), bilayer is formed inside the minicircle, resulting in DEB formation.
ssDNA minicircles react with complementary strands carrying alkyl groups in red thus forming (a.) a double-stranded DNA minicircle. In the presence of lipids (b.), bilayer is formed inside the minicircle, resulting in DEB formation.

Technology

DNA encircled bilayer (DEB) technology offers a means of producing size-controlled; planar lipid bilayers containing a defined number of membrane proteins reconstituted in a native membrane and encircled by a nucleic acid scaffold that is amenable to functionalization such as coupling of fluorophores or incorporation of sequence tags. The surrounding DNA circle is not limited by size thus even very large protein complexes may be accommodated. As the DNA scaffold is synthesized from commercially available components by standard chemical protocols (alkylation of phosphothioates), the technology allows for rapid prototyping, cost-efficiency and scalability.

Commercial Opportunity

Licensing and/or o-development.

Developmental Status

Prototype development / Validation phase.

Patent Situation

Priority patent application filed in 2018.

Further Reading

Iric, Fahmy, Schmidt et al., 2018. DNA-Encircled Lipid Bilayers. www.biorxiv.org/content/early/2018/03/21/285957