Page 260 - ebook

[D. Medicine/Translational Research] D-14

CRISPR-CasRx knockdown of pre-lamin A/progerin mRNA

in patient-derived fibroblast

Juyoung Hong¹, Junho Hur¹,²,³*

¹Department of Biomedical Science, Graduate School of Biomedical Science & Engineering, Hanyang University,
Seoul 04763, Korea, ²Department of Genetics, College of Medicine, Hanyang University, Seoul 04763, Korea,

³Department of Medicine, Graduate School, Hanyang University, Seoul 04763, Korea

The Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare and deadly genetic disease that exhibits premature
aging and cellular senescence. HGPS patients suffer from diverse senile diseases at an early age and pass away for

the most part from cardiovascular system complications around the age of 14. One of the prevalent causes of HGPS
is a genetic mutation in lamin A (LMNA), which is an essential element in the nuclear lamina. The introduction of a
de novo mutation in exon 11 of LMNA results in progerin proteins, an abnormal form of lamin A, which accumulates
progressively in the nuclear envelope. This affects even changes in the gene expression profile, such as the loss of

heterochromatin and genome instability. Currently, a study showed that in vivo base editing of mutant LMNA in the
HGPS mouse model ameliorated the sign of illness and extended the lifespan in mouse model. Nonetheless, CasRx

based gene therapy for HGPS in the human system has not been extensively investigated. Therefore, in this study,
we sought to apply CRISPR-CasRx for the knockdown of progerin mRNA in the HGPS patient-derived fibroblast to
advance the development of gene therapy for HGPS.