Page 25 - Q. Neuroscience

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 Seo, Eunna Chung, Junghwan Jo, Seungwoo Lee, Soyoung Park, Kangin Choi, Jaeheon Choi, Youngsil Choi and Daewoong Jo
Neurodegenerative Disease Drug Development Team, Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea

BACKGROUND AIM

The blood-brain barrier (BBB) is a tightly-regulated interface between neurons and blood The development of an efficient
vessels to control the neural delivery of systemically-circulated biomolecules and nutrients, therapeutic molecules for PD
which is a huge challenge for the development of biotherapeutics for neuro-disorders such as requires superior BBB-penetrating
Parkinson’s disease (PD) due to lack of BBB penetrability. capability.

METHODS

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). iCP-Parkin was detected in brain as assessed
by immunofluorescence, flow cytometry, LC-MS/MS, western blot and enzyme-linked immunosorbent assay (ELISA) analysis.

RESULTS

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, 700 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 CONCLUSION REFERENCES Contact information
accurately evaluate BBB-permeability and neuronal delivery of CP-proteins,
suggesting great applicability of aMTD in neuro-therapeutics. The current study can accurately evaluate Chung et al. (2020) Science Advances, 6: eaba 1193 Minyong Jung
BBB-permeability, deep tissue delivery Lim et al. (2013) Clinical Cancer Research, 19: 680-690 New Drug & Business Development
and neuronal delivery of CP-protein, Lim et al. (2013) Biomaterials, 34: 6261-6271 Cellivery Therapeutics, Inc.
suggesting great applicability of aMTD in Lim et al. (2012) Molecular Therapy, 20: 1540-1549
neuro-therapeutic agents. Jo et al (2005) Nature Medicine, 11: 892-898 jungmy@cellivery.com
+82-2-3151-8900
Jo et al (2001) Nature Biotechnology, 19: 929-933