Neural Noise

Computational modeling for conductivity-clamped gene electrotransfer in human striatum

2 min read

  • Bionic array-directed gene electrotransfer with conductivity-clamping was modeled using T1 and diffusion-weighted MRI and spatiotemporal CC mapping from guinea pig brain (Journal of Neural Engineering).1
  • Methodology is adjacent to neuromodulation and precision stimulation; gene therapy focus.1
  • Authors Keng-Yin Lai, Gary D. Housley, Nigel H. Lovell, Amr Al Abed and colleagues (UNSW Sydney / University of Sydney / Western Sydney University) developed a scalable computational model validated with both in vitro (HEK293 cells) and in vivo (guinea pig striatum) data.1
  • Conductivity-clamping (CC) works by displacing extracellular ionic species using a low-conductivity sucrose carrier solution infused near the electrodes; this increases local electric field strength while minimizing charge transfer, dramatically enhancing gene transfection efficiency without raising current to tissue-damaging levels.1
  • Key headline result: predicted suprathreshold brain tissue volume for gene electrotransfer in the human striatum increases by 130% with CC compared to standard GET, enabling far more precise and voluminous targeting of nucleic acid (DNA/mRNA) therapeutics.1
  • The model predicts transfection zone shape and volume as a function of GET pulse current amplitude, electrode orientation, and current steering — providing a design tool for clinical electrode placement and stimulation parameter selection.1
  • Primary clinical target is the striatal basal ganglia circuit in Parkinson’s disease; the technology offers a pathway for vector-free delivery of gene therapy payloads (naked plasmid DNA or mRNA) to deep brain structures currently requiring viral vectors or surgical implants.1
  • The BaDGE (Bionic array Directed Gene Electrotransfer) platform underlying this work has prior validation in cochlear gene therapy (regrowth of atrophied auditory nerve), demonstrating translational pathway from bionic-interface-adjacent ear to deep brain targets.2
  • The approach is complementary to deep brain stimulation (DBS): the same bionic electrode array used for chronic neural stimulation could in principle deliver gene therapy payloads at implant time or post-implant, merging stimulation and gene therapy into a single implanted device.2

Footnotes

  1. https://pubmed.ncbi.nlm.nih.gov/41757695/ ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7

  2. https://www.unsw.edu.au/medicine-health/our-schools/biomedical-sciences/research-and-impact/showcase/bionic-array-directed-gene-electrotransfer-badge ↩ ↩2

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