Microbubble-facilitated ultrasound pulsation promotes direct α-synuclein gene delivery

Chia Jung Lin, Chung Yin Lin, Ya Tin Lin, Chiung Yin Huang, Kuo Chen Wei, Jin Chung Chen, Guey Jen Lee-Chen, Hao Li Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Intra-neuronal α-synuclein (αSNCA) aggregation are the leading cause of dopaminergic neuron degeneration in Parkinson's disease (PD). Most PD patients is linked with αSNCA gene mutations. Gene therapy shows therapeutic potential by packing gene into viral vectors to improve gene expression through stereotactic brain injections. However, through intracranial injection, the gene expression is typically limited with tissue distribution tightly adjacent to the injection track, when expressing therapeutic genes for a wider CNS region is preferable. We use microbubble-facilitated ultrasound pulsations (MB-USP) as a new gene delivering tool to enhance the limit gene delivery of local injection in brain and evaluate the feasibility using αSNCA as model gene. We demonstrate that MB-USP can transfect naked constructs DNA of αSNCA gene into two types of neuron cells and enhance the gene expression. We confirm α-synuclein fusion protein functionality, showing that α-synuclein fusion protein significantly reduce the mitochondrial activity. We show MB-USP improves in vivo gene transfer in the brain with naked construct local injection, significantly enhances α-synuclein expression level to 1.68-fold, and broaden its distribution to 25-fold. In vivo fused α-synuclein protein aggregation is also found in gene-injected mice brains by MB-USP. MB-USP provides an alternative to α-synuclein over expression in vitro and in vivo model for investigation of α-synuclein related PD therapeutic strategies.

Original languageEnglish
Pages (from-to)77-83
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 2019 Sept 10


  • Focused ultrasound
  • Gene therapy
  • Microbubble
  • Parkinson's disease
  • α-synuclein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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