Repository logo
 
Publication

From bench to bioterium and back again: development of a U1snRNA-based therapeutic strategy for mucopolysaccharidosis IIIC

2020-11Conference object Open access
Simple item page
dc.contributor.authorSantos, Juliana Inês
dc.contributor.authorMatos, Liliana
dc.contributor.authorOliveira, Paula Alexandra
dc.contributor.authorGonçalves, Mariana
dc.contributor.authorPires, Maria João
dc.contributor.authorCoutinho, Maria Francisca
dc.contributor.authorPrata, Maria João
dc.contributor.authorAlves, Sandra
dc.date.accessioned2021-03-13T16:29:37Z
dc.date.available2021-03-13T16:29:37Z
dc.date.issued2020-11
dc.description.abstractSplicing is an essential cellular process to generate mature transcripts from pre-mRNA. One of the most important factors for mRNA transcription is the U1snRNA, a spliceosomal component that recognizes 5’ splicing donor sites (SDS) at specific regions in pre-mRNA. Splicing mutations represent one of the most frequent (~20%) genetic defects in Mucopolysaccharidosis IIIC (MPS IIIC), a Lysosomal Storage Disorder (LSD) caused by mutations in the HGSNAT gene, encoding an enzyme involved in heparan sulphate degradation. . Exon-skipping has been demonstrated as, probably, the most frequent aberrant splicing defect, and occurs due to mutations in the 5’ SDS. Application of modified U1snRNAs to improve recognition of mutated 5’ SDS represent a potential therapeutic strategy to recover the normal splicing process. The c.234+1G>A is a frequent mutation among patients of countries around the Mediterranean basin (Portugal, Spain, Morocco and Tunisia). It’s located in the + 1 position of intron 2 of HGSNAT gene and leads to the skipping of exon 2. We demonstrated in fibroblast cells that a modified U1snRNA vector (comprising exon 1 to exon 3) designed to improve the definition of exon 2 5’ SDS of the HGSNAT can restore the splicing defect caused by the mutation c.234+1G>A (Matos et al., 2014). Currently our goal is to evaluate in vivo the therapeutic potential of the modified U1 snRNA by testing it in mice expressing the human splicing defect.pt_PT
dc.description.sponsorshipFCTpt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/7462
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectLysosomal Storage Diseasespt_PT
dc.subjectRNA Therapiespt_PT
dc.subjectDoenças Lisossomais de sobrecargapt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectTerapias de RNApt_PT
dc.titleFrom bench to bioterium and back again: development of a U1snRNA-based therapeutic strategy for mucopolysaccharidosis IIICpt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceGeneva, Suiça (online)pt_PT
oaire.citation.title3rd International Conference on Sanfilippo Syndrome and Related Diseases, 12-13 November 2020pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Santos JI (SanfilippoSuisse).pdf
Size:
1.02 MB
Format:
Adobe Portable Document Format
Download

Collections

DGH - Posters/abstracts em congressos internacionais