RT Journal Article
SR Electronic
T1 Uncovering temporally sensitive targeting motifs for traumatic brain injury via phage display
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.16.155325
DO 10.1101/2020.06.16.155325
A1 Briana I. Martinez
A1 Gergey Alzaem Mousa
A1 Kiera Fleck
A1 Tara MacCulloch
A1 Chris W. Diehnelt
A1 Nicholas Stephanopoulos
A1 Sarah E. Stabenfeldt
YR 2020
UL http://biorxiv.org/content/early/2020/06/17/2020.06.16.155325.abstract
AB The heterogeneous injury pathophysiology of traumatic brain injury (TBI) is a barrier to developing highly sensitive and specific diagnostic tools. Embracing neural injury complexity is critical for the development and advancement of diagnostics and therapeutics. The current study employs a unique discovery pipeline to identify targeting motifs that recognize specific phases of TBI pathology. This pipeline entails in vivo biopanning with a domain antibody (dAb) phage display library, next generation sequencing (NGS) analysis, and peptide synthesis. Here, we identify targeting motifs based on the HCDR3 structure of dAbs for acute (1 day) and subacute (7 days) post-injury timepoints using a mouse controlled cortical impact model. Their bioreactivity was validated using immunohistochemistry and candidate target epitopes were identified via immunoprecipitation-mass spectrometry. The acute targeting motif recognizes targets associated with metabolic and mitochondrial dysfunction whereas the subacute motif was largely associated with neurodegenerative processes. This phage display biomarker discovery pipeline for TBI successfully achieved discovery of temporally specific TBI targeting motif/epitope pairs that will advance the TBI diagnostics and therapeutics.Competing Interest StatementThe authors have declared no competing interest.