Generation of a Beta-Cell Transplant Animal Model of Diabetes Using CRISPR Technology.
Beta Cells
CRISPR/Cas9
Insulin Gene Therapy
Lentivirus
Journal
Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103
Informations de publication
Date de publication:
2023
2023
Historique:
pubmed:
27
10
2022
medline:
25
3
2023
entrez:
26
10
2022
Statut:
ppublish
Résumé
Since insulin deficiency results from pancreatic beta-cell destruction, all type 1 and most type 2 diabetes patients eventually require life-long insulin injections. Insulin gene synthesis could also be impaired due to insulin gene mutations as observed in diabetic patients with MODY 10. At this point, insulin gene therapy could be very effective to recompense insulin deficiency under these circumstances. For this reason, an HIV-based lentiviral vector carrying the insulin gene under the control of insulin promoter (LentiINS) was generated, and its therapeutic efficacy was tested in a beta-cell transplant model lacking insulin produced by CRISPR/Cas9-mediated genetically engineered pancreatic beta cells. To generate an insulin knockout beta-cell transplant animal model of diabetes, a dual gene knockout plasmid system involving CRISPR/Cas9 was transfected into a mouse pancreatic beta cell line (Min6). Fluorescence microscopy and antibiotic selection were utilized to select the insulin gene knockout clones. Transplantation of the genetically engineered pancreatic beta cells under the kidney capsule of STZ-induced diabetic rats revealed LentiINS- but not LentiLacZ-infected Ins2KO cells transiently reduced hyperglycemia similar to that of MIN6 in diabetic animals. These results suggest LentiINS has the potential to functionally restore insulin production in an insulin knockout beta-cell transplant animal model of diabetes.
Identifiants
pubmed: 36289162
doi: 10.1007/5584_2022_746
doi:
Substances chimiques
Insulin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
145-159Informations de copyright
© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.
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