A Multifunctional Aptamer Decorated Lipid Nanoparticles for the Delivery of EpCAM-targeted CRISPR/Cas9 Plasmid for Efficacious In Vivo Tumor Regression

Sarkar, S and Moitra, P and Duan, W and Bhattacharya, S (2024) A Multifunctional Aptamer Decorated Lipid Nanoparticles for the Delivery of EpCAM-targeted CRISPR/Cas9 Plasmid for Efficacious In Vivo Tumor Regression. In: Advanced Healthcare Materials .

PDF Adv_Hea__Mat_2024.pdf - Published Version Restricted to Registered users only Download (10MB) | Request a copy

Abstract

Epithelial cell adhesion molecule (EpCAM) gene encodes a type-I trans-membrane glycoprotein that is overexpressed in many cancerous epithelial cells and promotes tumor progression by regulating the expression of several oncogenes like c-myc and other cyclins. Because of this tumorigenic association, the EpCAM gene has been a potential target for anti-cancer therapy in recent days. Herein, it is attempted to knockout the proto-oncogenic EpCAM expression by efficiently delivering an all-in-one Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) plasmid via a lipid nanoparticle system made out of synthetic stimuli-sensitive lipids. The plasmid possesses the necessary information in the form of a guide RNA targeted to the EpCAM gene. The aptamer decorated system selectively targets EpCAM overexpressed cells and efficiently inhibits the genetic expression. It has explored the pH-responsive property of the developed lipid nanoparticles and monitored their efficacy in various cancer cell lines of different origins with elevated EpCAM levels. The phenomenon has further been validated in vivo in non-immunocompromised mouse tumor models. Overall, the newly developed aptamer decorated lipid nanoparticle system has been proven to be efficacious for the delivery of EpCAM-targeted CRISPR/Cas9 plasmid. © 2024 Wiley-VCH GmbH.

Item Type:	Journal Article
Publication:	Advanced Healthcare Materials
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright for this article belongs to Advanced Healthcare Materials.
Keywords:	Cell adhesion; Cell culture; Gene encoding; Gene expression regulation; Gene therapy; Glycoproteins; Nanoparticles; Oncogenic viruses, Anti-tumor therapeutic; Anti-tumors; Cellular migration; Clustered regularly interspaced short palindromic repeat/cas9 all-in-one plasmid; Epithelial cell adhesion molecule; Epithelial cell adhesion molecules; Lipid nanoparticles; Metastasis; Palindromic; Transfection, Gene expression
Department/Centre:	Division of Chemical Sciences > Organic Chemistry
Date Deposited:	13 Sep 2024 04:37
Last Modified:	13 Sep 2024 04:37
URI:	http://eprints.iisc.ac.in/id/eprint/86130

Actions (login required)

View Item