Ion Channel scFv Library

A synthetic phage display library, the Twist Ion Channel scFv Library transplants loop sequences from natural peptide toxins of spiders, snakes, scorpions, and sea anemones into the HCDR3 of the Twist GPCR 2.0 scFv Library, a diverse human scFv antibody library. This allows the library to mimic the binding of peptide neurotoxins to ion channel targets. When introduced into two heavy chains (VH1-69 and VH3-30) and four light chains (VK1-39, VL1-51, VL2-14, VK3-15), combinatorial assembly generates a fully human scFv phage display library with a diversity of 1 x 10⁹.

Twist offers two formats within the Ion Channel scFv Library: one with paired cysteines (Cys+ library), which can form intramolecular disulfide bonds to lock in the structure, and one without the cysteine pair (Cys- library). The Cys+ library incorporates the cysteine residues on the N- and C-terminal ends of the HCDR3 loop. Both formats are provided as a part of the Ion Channel scFv Library and can be panned in parallel against your target of interest.

The Cys+ and Cys- libraries draw their CDR3 diversity from 2,219 loops (length: 11–78 amino acids) and 1,852 loops (length: 9–66 amino acids), respectively. Each CDR3 loop is flanked by flexible GSG linkers and excludes unpaired C- and N-glycosylation sites.

Go from panning to functional assays in 10–12 weeks.

The process starts with phage screening the diverse Twist Ion Channel scFv Library against target antigens and ends with reformatting candidate antibody fragments to full-length IgG.

You can also license the Ion Channel scFv library to initiate your own in-house discovery projects. To learn more, get in touch at biopharma@twistbioscience.com.

The Twist Ion Channel scFv Library was successfully panned against APJR, a multi-pass transmembrane receptor, to identify multiple unique clones that bind this cardiovascular target. Flow titration demonstrates that antibodies, like SC-44-139, bind APJR+ positive cells with high affinity.