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Idea – IND

BBB Shuttle Engineering

HCAb-derived shuttle systems engineered for receptor-mediated CNS transport

Overview
Shuttle Engineering
Applications

Overcoming the CNS Delivery Challenge

The blood-brain barrier (BBB) significantly restricts delivery of biologics into the central nervous system (CNS), limiting therapeutic development across neurodegenerative disease, brain oncology, and other neurological disorders.

Nona Biosciences leverages fully human heavy chain-only antibody (HCAb) technologies to engineer BBB shuttle systems capable of facilitating receptor-mediated transport across targets such as TfR1, CD98, and IGFR1 while maintaining developability and manufacturability.

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Engineering BBB Transport Systems

Using Harbour Mice® HCAb platforms, Nona Biosciences develops affinity-optimized binders designed to support efficient CNS transport while balancing receptor engagement, tissue penetration, and downstream therapeutic distribution.

Capabilities include:

  • Affinity tuning
  • BBB shuttle bispecific engineering
  • HCAb-derived CNS delivery formats
  • Brain penetration assessment
  • CNS pharmacokinetic characterization
  • Cross-species binder generation

Improving Brain Penetration

Optimizing binding affinity is critical for achieving effective receptor-mediated transcytosis across the BBB. HCAb-derived transport systems with tunable affinity profiles are designed to support:

  • Improved brain exposure
  • Enhanced parenchymal distribution
  • Reduced peripheral sequestration
  • Optimized pharmacokinetics

Expanding CNS Delivery Across Therapeutic Modalities

HCAb-enabled CNS transport strategies support delivery across diverse therapeutic applications and cargo formats. Engineering workflows balance receptor engagement and CNS transport efficiency to support a broad range of therapeutic modalities while maintaining effective brain exposure and distribution.

Applications include:

  • Neurodegeneration
  • Brain oncology
  • Lysosomal storage disorders
  • CNS-targeted ADCs
  • RNA delivery
  • Enzyme replacement
  • CNS immune modulation

Compatible cargo systems may include:

  • Bispecific antibodies
  • Oligonucleotides
  • RNA delivery systems and LNPs
  • T cell engagers
  • Fusion proteins

Explore CNS Delivery Strategies

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Explore Related Resources

HCAb Platform Whitepaper
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