Design of Nanocarriers for Kidney Targeted Delivery of Nucleic Acid Therapeutics.

Driven by recent successful clinical translation, nucleic acid therapeutics are being actively investigated to expand their applications to various diseases, including renal genetic disorders. As life expectancy increases and the burden of renal diseases continues to rise, nucleic acid therapeutics are considered promising alternatives to conventional treatments. This review summarizes key considerations in the design and fabrication of nanocarriers for the systemic delivery of nucleic acid therapeutics to the kidneys. Key aspects of the renal microenvironment are discussed to guide the design of nanocarriers, including conjugates and nanoparticles. This review also covers renal genetic disorders and nucleic acid-based treatment approaches, including small interfering RNAs (siRNAs), clustered regularly interspaced short palindromic repeats (CRISPR) systems, and messenger RNA (mRNA) therapeutics. In particular, recent strategies for kidney-targeted nanocarriers are highlighted, with an emphasis on their efficacy, challenges, and limitations. Perspectives on the design of nanocarriers for systemic nucleic acid delivery to the kidneys are also provided, offering insights into potential therapeutic approaches for renal genetic disorders.