Page 1 - P. Molecular medicine and imaging

Cell-Permeable Frataxin (CP-FXN) Ameliorate The Symptoms Of
Friedreich’s Ataxia Through Regulation Of Cellular Iron Metabolism

Joonno Lee, Sookeun Yeon, Wonheum Nah, Jeongheon Choi, Sujung Lee, Sunwoong Kim,Youngsil Choi and Daewoong Jo
FXN Team, Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea

BACKGROUND AIM

Friedreich’s ataxia (FRDA) is monogenic autosomal recessive disease causing To ameliorate FRDA symptoms, cell-permeable FXN
neurodegeneration and cardiomyopathy. FRDA is attributed to depletion of the (CP-FXN) has been developed by fusing sequence-
mitochondrial protein frataxin (FXN), which is caused by a GAA expansion in first optimized advanced macromolecule transduction
intron of the frataxin gene. FXN is known to play a key role in iron metabolism in iron- domain (aMTD) to deliver FXN directly into cells and
sulfur cluster (ISC) biogenesis and heme biosynthesis, both of which occur in tissues.
mitochondria.
METHODS
A structurally stable backbone for CP-FXN has been established by examining structural stability and biological activity of various recombinant
proteins. Next, to optimize the activity of FXN candidates, advanced macromolecule transduction domains (aMTDs) were screened for
enhanced solubility, biological activity, and cell permeability.
RESULTS

Figure 1. Development Of Structurally Stable Figure 2. Structure, Homogeneity & Figure 6. CP-FXN Interacts
aMTD/SD-Fused FXM Recombinant Protein CD Analysis Of CP-FXN With Fe & Blocks Iron-Accumulation
2+
A A D A
B C 100% 95%

B

Figure 3. CP-FXN Is Intracellularly Delivered
A B
B C
5770%

C Figure 4. CP-FXN Is Co-Localized D
With Mitochondria 84%
A B

D Figure 7. CP-FXN Restores Aconitase &
Figure 5. CP-FXN Is Intracellularly SDH Activity In FXN-Knockdowned Cells
Distributed In Brain and Heart A
A 110% 87%
700%

800%
E
B
70% 68%
B C 100% 51% 55%

CONCLUSION REFERENCES Contact Information

CP-FXN is delivered into mitochondria, blocks iron Chung et al. (2020) Science Advances, 6: eaba 1193 Minyong Jung
accumulation by binding to iron and restores Lim et al. (2013) Clinical Cancer Research, 19: 680-690 New Drug & Biusiness Development
activity of ISC-dependent aconitase in FXN Lim et al. (2013) Biomaterials, 34: 6261-6271
deficient cells. Based on these data, CP-FXN has Lim et al. (2012) Molecular Therapy, 20: 1540-1549 Cellivery Therapeutics Inc.
a therapeutic potential for FRDA treatment Jo et al. (2005) Nature Medicine, 11: 892-898 jungmy@cellivery.com
through mitochondrial delivery. +82-2-3151-8900
Jo et al. (2001) Nature Biotechnology, 19:929-933