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Antisense Oligonucleotide (ASO) Conjugated With Cell-Penetrating Peptide
Effectively Reduces Target Gene Via Direct Penetration And Cell-To-Cell Transfer

Seulmee Shin, Youngjin Seo, Shinyoung Kang, Youlim Hong, Wookyung Kang, Eunna Chung and
Daewoong Jo
Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea
BACKGROUND AIM

Antisense oligonucleotide (ASO) is one of the RNA-therapeutics based on RNaseH- To enhance the systemic delivery of ASO via direct
mediated cleavage and subsequent degradation of complementary RNAs. In the penetration and cell-to-cell transfer, cell-penetrating
bench-top research, the endocytic delivery of ASO into a single-cell level is possible, peptides (CPPs) named advanced macromolecule
which is limited for in-vivo ASO delivery in a multicellular and systemic environment, transduction domain (aMTD) have been applied.
leading to clinical application.
METHODS
Therapeuticmolecule systemic delivery technology (TSDT) enabled with sequence optimized aMTD provides a solution to ASO. In a sequential
aMTD screening steps, the best construct for cell-permeable ASO (CP-ASO) was selected. The knockdown (KD) activity of ASO conjugated with
aMTDs (CP-ASO) was evaluated by using qPCR.

RESULTS

CONCLUSION REFERENCES CONTACT INFORMATION

CP-ASO showed significant KD activity, Chung et al. (2020) Science Advances, 6: eaba 1193 Seulmee Shin, Ph.D
indicating that aMTD facilitates the Lim et al. (2013) Clinical Cancer Research, 19: 680-690
intracellular delivery of ASO via direct Lim et al. (2013) Biomaterials, 34: 6261-6271 Cellivery Therapeutics, Inc.
penetration rather than endocytosis. CP-ASO shinsm@cellivery.com
can be delivered via cell-to-cell transfer. CP- Lim et al. (2012) Molecular Therapy, 20: 1540-1549
ASO has the potential to be used as a new Jo et al. (2005) Nature Medicine, 11: 892-898 +82-2-3151-8900
practical paradigm for RNA-therapeutics. Jo et al. (2001) Nature Biotechnology, 19: 929-933 S4-3 신진과학자