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Engineering lentivirus envelope VSV-G for liver targeted delivery of IDOL-shRNA to ameliorate hypercholesterolemia and atherosclerosis
- Source :
- Molecular Therapy: Nucleic Acids, Vol 35, Iss 1, Pp 102115- (2024)
- Publication Year :
- 2024
- Publisher :
- Elsevier, 2024.
-
Abstract
- Lentiviral vectors (LVs) have been widely used as a tool for gene therapies. However, tissue-selective transduction after systemic delivery remains a challenge. Inducible degrader of low-density lipoprotein receptor is an attractive target for treating hypercholesterolemia. Here, a liver-targeted LV, CS8-LV-shIDOL, is developed by incorporating a hepatocyte-targeted peptide derived from circumsporozoite protein (CSP) into the lentivirus envelope for liver-targeted delivery of IDOL-shRNA (short hairpin RNA) to alleviate hypercholesterolemia. Tail-vein injection of CS8-LV-shIDOL results in extremely high accumulation in liver and nearly undetectable levels in other organs in mice. In addition, it shows superior therapeutic efficacy in lowering serum low-density lipoprotein cholesterol (LDL-C) and reducing atherosclerotic lesions over unmodified LV-shIDOL in hyperlipidemic mice. Mechanically, the envelope-engineered CS8-LV-shIDOL can enter liver cells via low-density lipoprotein receptor-related protein (LRP). Thus, this study provides a novel approach for liver-targeted delivery of IDOL-shRNA to treat hypercholesterolemia by using an envelope-engineered LV, and this delivery system has great potential for liver-targeted transgene therapy.
Details
- Language :
- English
- ISSN :
- 21622531
- Volume :
- 35
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Molecular Therapy: Nucleic Acids
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.9b3fd0aeb11241bf9ba95f222b92724b
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.omtn.2024.102115