Dynamics within supramolecuar IKVAV matrices enhance functional maturation of human IPSCS-derived neurons and regeneration
Inventors
Pinto, Zaida Alvarez • Sato, Kohei • Ortega Cano, Juan Alberto • Kiskinis, Evangelos • Stupp, Samuel I.
Assignees
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Publication Number
US-12552833-B2
Publication Date
2026-02-17
Expiration Date
Abstract
Provided herein are peptide amphiphiles (PAs) comprising a bioactive peptide, nanofibers displaying the bioactive PAs, and methods of use thereof. The disclosed peptide amphiphiles comprise a hydrophobic tail, a structural peptide segment, a charged peptide segment, and a bioactive IKVAV peptide. The disclosed PAs may be used in cell culture methods and in methods of treating central nervous system injury.
Core Innovation
The invention relates to IKVAV (SEQ ID NO:25)-bioactive peptide amphiphiles and their nanofibers. The peptide amphiphile includes a hydrophobic alkyl tail having an 8-24 carbon alkyl chain (C8-24), a structural peptide segment comprising SEQ ID NO:1, and a charged peptide segment comprising EE, EEE, or SEQ ID NO:5. The bioactive peptide is provided as IKVAV (SEQ ID NO:25), optionally attached via a linker such as a single glycine.
The disclosed IKVAV-bioactive peptide amphiphiles form nanofibers. In addition, the nanofibers may include filler peptide amphiphiles that lack the bioactive moiety in order to tune mechanics and gel/liquid behavior with pH. The invention also includes supramolecular IKVAV matrices in the context of neuronal culture and central nervous system injury treatment.
The document further describes exemplary peptide amphiphiles and their sequences, including C16V2A2E4GIKVAV (SEQ ID NO:6), C16A2G2E4GIKVAV (SEQ ID NO:7), and C16VEVA2E4GIKVAV (SEQ ID NO:8). It also describes characterization and analysis including TEM/cryo-TEM/SEM, AFM, WAXS/IR, LC-MS, and rheology, together with cell and in vivo applications involving hiPSC-derived motor neurons and a mouse spinal cord injury model.
Claims Coverage
The independent claim covers a peptide amphiphile with a hydrophobic alkyl tail (C8-24), a structural peptide segment (SEQ ID NO:1), a charged peptide segment (EE, EEE, or SEQ ID NO:5), and a bioactive peptide. The claim set includes dependent refinements that specify IKVAV (SEQ ID NO:25), attachment via a linker, and particular sequence/structure combinations, and further extends coverage to nanofibers optionally with filler peptide amphiphiles lacking a bioactive moiety and pharmaceutical compositions comprising the nanofiber.
Peptide amphiphile architecture with C8-24 hydrophobic tail, structural and charged peptide segments, and a bioactive peptide
A peptide amphiphile comprising a hydrophobic tail comprising an 8-24 carbon alkyl chain (C8-24), a structural peptide segment comprising SEQ ID NO:1, a charged peptide segment comprising EE, EEE, or SEQ ID NO:5, and a bioactive peptide.
IKVAV bioactive peptide
The peptide amphiphile includes a bioactive peptide corresponding to SEQ ID NO:25.
Bioactive peptide attached to charged peptide segment via a linker
The bioactive peptide is attached to a charged peptide segment via a linker.
Particular sequence and structure combination
The peptide amphiphile is defined to comprise C8-24 and SEQ ID NO:7.
Nanofiber comprising the peptide amphiphile
A nanofiber comprising the peptide amphiphile defined in claim 1.
Nanofiber including filler peptide amphiphiles lacking a bioactive moiety
The nanofiber includes one or more filler peptide amphiphiles with a hydrophobic tail, a structural peptide segment, and a charged peptide segment, and lacking a bioactive moiety.
Overall, the claim coverage centers on an IKVAV-bioactive peptide amphiphile architecture with defined hydrophobic, structural, and charged segments, including options for IKVAV specificity, linker attachment, and defined sequence combinations. It further covers assemblies as nanofibers, optionally containing filler peptide amphiphiles lacking a bioactive moiety, with extension to pharmaceutical compositions recited for the nanofiber.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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