Future perspectives using Lysosomal Storage Disease iPSCs models and gene editing therapy

Ribeiro, Diogo; Duarte, Ana Joana; Amaral, Olga

http://hdl.handle.net/10400.18/8139

Use this identifier to reference this record.

Name:	Description:	Size:	Format:
Poster_ ciencia21_Diogo_Joana - olga july21.jpg		2.17 MB	JPEG	Download

Send Feedback

Authors

Ribeiro, Diogo

Duarte, Ana Joana

Amaral, Olga

Abstract(s)

Lysosomal storage diseases (LSDs) are characterized by accumulation of macromolecules in the late endocytic system. Their collective frequency of 1/5000 live births and are caused by inherited defects in genes that mainly encode lysosomal proteins (1). In the Portuguese population, lysosomal storage disorders (LSDs) have a prevalence of 1/4000 live births. Tay Sachs disease (TSD, MIM#272800) variant B1 is one of the most prevalent in the Portuguese population (2). The TSD variant B1 is caused by mutations on the HEXA gene (MIM#606869.0006), leading to hexosaminidase A malfunction. The mutation subject of this study, p.R178H (rs28941770), is frequent in specific populations. In the Portuguese it has a carrier frequency of 1:340, and in the North of Portugal it was estimated to be 1:119. Fabry disease ((FD, MIM#301500)) is one of the most frequent LSDs, it is caused by mutations on the GLA gene (MIM#300644), such as the mutation p.W287X (rs104894839), leading to alpha-galactosidase A impairment. Gaucher disease (GD) is also a frequent LSD and it is, usually, due to deficient activity of lysosomal acid beta glucosidase (GBA1, MIM#606463). It has several phenotypic forms (GD1, 230800; GD2, 230900; and GD3; 231000) of which the most severe are neurodegenerative and elude common therapies. In our group, we are attempting to use gene editing through CRISPR/Cas9 as a therapeutic tool to correct specific mutations involved in the abovementioned diseases. Our aim is first to obtain induced pluripotent stem cells (iPSCs) derived from these cell lines and then to correct the mutational defects.

Description

Trabalho iniciado no âmbito de PTDC/BIM-MEC/4762/2014 (2016-2020) e de doutoramentos na UP (ICBAS) de Diogo Ribeiro e Ana Joana Duarte (co-1º autores)