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CRISPR/Cas9 as a to...
CRISPR/Cas9 as a tool to disrupt wild-type and A53T SNCA in sporadic and familial Parkinson’s disease
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- Molisak, Agnieszka (författare)
- Uppsala universitet,Geriatrik,Molekylär geriatrik, Molecular Geriatrics
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- Konstantinidis, Evangelos, 1990- (författare)
- Uppsala universitet,Geriatrik,Molekylär geriatrik, Molecular Geriatrics
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- Aguilar, Ximena (författare)
- Uppsala universitet,Geriatrik,Molekylär geriatrik, Molecular Geriatrics
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- Giedraitis, Vilmantas (författare)
- Uppsala universitet,Geriatrik,Molekylär geriatrik, Molecular Geriatrics
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- Stefanis, Leonidas (författare)
- Biomedical Research Foundation Academy of Athens, Center of Clinical, Experimental Surgery & Translational Research, Athens, Greece
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- Vekrellis, Kostas (författare)
- Biomedical Research Foundation Academy of Athens, Center of Clinical, Experimental Surgery & Translational Research, Athens, Greece
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- Ramachandran, Mohanraj, 1988- (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi
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- Sarén, Tina (författare)
- Uppsala universitet,Klinisk immunologi
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- Erlandsson, Anna (författare)
- Uppsala universitet,Geriatrik,Molekylär geriatrik, Molecular Geriatrics
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- Mary, Bertin (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- György, Bence (författare)
- University of Basel, Department of Ophthalmology, Basel, Switzerland
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- Essand, Magnus (författare)
- Uppsala universitet,Klinisk immunologi,Enheten för klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Ingelsson, Martin (författare)
- Uppsala universitet,Geriatrik,Molekylär geriatrik, Molecular Geriatrics
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Parkinson’s Disease (PD) is characterized by pathological accumulation of α-synuclein (αSyn) as Lewy bodies and Lewy neurites in the brain. Current treatment strategies can only alleviate the symptoms but do not interfere with the disease progression. With the discovery of the CRISPR/Cas9 gene editing tool, it has become possible to target the generation of pathological protein aggregates at the DNA level. Disrupting the αSyn gene (SNCA) could prevent the formation of Lewy-related pathologies. Here, we have designed two CRISPR/Cas9-based approaches by using guide RNAs (gRNAs) that are targeting either wild-type (WT) SNCA (pan-SNCA) or mutant A53T SNCA that causes early-onset familial PD. We could demonstrate that plasmid vector-mediated transfection of the pan-SNCA gRNA led to robust allelic disruption in HEK293T cells and human fibroblasts and that the editing efficiency was further increased with the use of a lentiviral transduction system. In addition, the SNCA A53T gRNA was specific towards the mutation site, but resulted in low and inconsistent targeting efficiencies in human patient fibroblasts carrying the SNCA A53T mutation. Our results indicate that SNCA can be targeted by CRISPR/Cas9, although the system efficiency varies across different cell types. In the future, systemically administered gene-editing treatments based on CRISPR/Cas9 could provide a valid therapeutic approach for PD patients.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Parkinson's disease
- alpha-synuclein
- gene editing
- crispr
- cas9
- fibroblasts
- lentivirus
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)
- Av författaren/redakt...
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Molisak, Agniesz ...
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Konstantinidis, ...
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Aguilar, Ximena
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Giedraitis, Vilm ...
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Stefanis, Leonid ...
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Vekrellis, Kosta ...
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visa fler...
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Ramachandran, Mo ...
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Sarén, Tina
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Erlandsson, Anna
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Mary, Bertin
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György, Bence
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Essand, Magnus
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Ingelsson, Marti ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Av lärosätet
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Uppsala universitet