Page 26 - Q. Neuroscience

[Q. Neuroscience-15]

A smart delivery of drugs into neurons: a novel cell-

penetrating peptide enables therapeutic protein to meet

intracellular targets in the interface of blood-brain barrier

Youngjin Seo¹, Eunna Chung¹, Junghwan Jo¹, Seungwoo Lee¹, Soyoung Park¹, Kangin Choi¹, Jaeheon Choi¹,

Youngsil Choi¹, Daewoong Jo¹˙*

¹R&D, Cellivery therapeutics, Inc., Seoul 03929, Korea

The blood-brain barrier (BBB) is a tightly-regulated interface between neurons and blood vessels to control the

neural delivery of systemically-circulated biomolecules and nutrients, which is a huge challenge for the development
of biotherapeutics for neuro-disorders such as Parkinson’s disease (PD) due to lack of BBB penetrability. Effective

treatment of therapeutic molecules for PD requires superior BBB-penetrating capability. Here, brain
pharmacokinetics (PK) studies have being performed in order to demonstrate neuronal delivery of cell-permeable

(CP) proteins fused to a sequence-optimized advanced macromolecule transduction domain (aMTD). This study
shows that the tissue-permeability of aMTD-fused Parkin (iCP-Parkin) was significantly promoted in 6 major organs

including brain. The quantitative analysis showed that iCP-Parkin was rapidly delivered into the deep brain (LC-
MS/MS, 400 ng/g) and iCP-Parkin signals inside neurons were strongly detected by immunofluorescent analysis

after intravenous injection (100 mg/kg), which is currently being examined by using immune magnetically isolated
neurons from brain. In overall, the current study can accurately evaluate BBB-permeability and neuronal delivery of

CP-proteins, suggesting great applicability of aMTD in neuro-therapeutics.