Targeting strategies with lipid vectors for nucleic acid supplementation therapy in Fabry disease: a systematic review.

Autor: Rodríguez-Castejón J; Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country, UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz, 01006, Spain.; Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents and Gene Therapy, Vitoria-Gasteiz, 01006, Spain., Beraza-Millor M; Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country, UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz, 01006, Spain.; Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents and Gene Therapy, Vitoria-Gasteiz, 01006, Spain., Solinís MÁ; Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country, UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz, 01006, Spain.; Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents and Gene Therapy, Vitoria-Gasteiz, 01006, Spain., Rodríguez-Gascón A; Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country, UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz, 01006, Spain.; Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents and Gene Therapy, Vitoria-Gasteiz, 01006, Spain., Del Pozo-Rodríguez A; Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country, UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz, 01006, Spain. ana.delpozo@ehu.eus.; Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents and Gene Therapy, Vitoria-Gasteiz, 01006, Spain. ana.delpozo@ehu.eus.
Jazyk: angličtina
Zdroj: Drug delivery and translational research [Drug Deliv Transl Res] 2024 Oct; Vol. 14 (10), pp. 2615-2628. Date of Electronic Publication: 2024 Apr 08.
DOI: 10.1007/s13346-024-01583-0
Abstrakt: Fabry disease (FD) results from a lack of activity of the lysosomal enzyme α-Galactosidase A (α-Gal A), leading to the accumulation of glycosphingolipids in several different cell types. Protein supplementation by pDNA or mRNA delivery presents a promising strategy to tackle the underlying genetic defect in FD. Protein-coding nucleic acids in FD can be either delivered to the most affected sites by the disease, including heart, kidney and brain, or to specialized organs that can act as a production factory of the enzyme, such as the liver. Lipid-based systems are currently at the top of the ranking of non-viral nucleic acid delivery systems, and their versatility allows the linking to the surface of a wide range of molecules to control their biodistribution after intravenous administration. This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines and provides an overview and discussion of the targeting ligands that have been employed so far to actively vectorize intravenously administered non-viral vectors based on lipid carriers to clinically relevant organs in the treatment of FD, for protein-coding nucleic acid (pDNA and mRNA) supplementation. Among the thirty-two studies included, the majority focus on targeting the liver and brain. The targeting of the heart has been reported to a lesser degree, whereas no articles addressing kidney-targeting have been recorded. Although a great effort has been made to develop organ-specific nucleic acid delivery systems, the design of active-targeted carriers with high quality, good clinical translation, and large-scale manufacturing capacity is still challenging.
(© 2024. The Author(s).)
Databáze: MEDLINE
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