Polycystin-1 (PKD1) mRNA (PKD1 mRNA)

PKD1 mRNA is the transcript of the Polycystic Kidney Disease 1 gene, which encodes the large transmembrane protein Polycystin-1 (PC1). PC1 is localized to the primary cilia and plasma membrane of renal epithelial cells, where it functions as a mechanosensor and regulator of calcium signaling and cell proliferation (UniProt P98161). Mutations in PKD1 are responsible for approximately 85% of cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD), a condition characterized by the progressive development of numerous fluid-filled cysts that eventually lead to end-stage renal disease (NIH/NIDDK, 2023). Therapeutic strategies targeting PKD1 mRNA aim to restore functional PC1 levels, either by delivering exogenous mRNA via lipid nanoparticles or by using antisense oligonucleotides to inhibit microRNAs, such as miR-17, that suppress the translation of endogenous PKD1 transcripts (Regulus Therapeutics, 2024; ReCode Therapeutics, 2023). Increasing the expression of functional PKD1 mRNA is expected to normalize cellular signaling, reduce cyst growth, and preserve kidney function. However, challenges include the massive size of the PKD1 transcript (approximately 14 kb) and the need for targeted delivery to the renal tubular epithelium to avoid systemic side effects.

Other names

Polycystic kidney disease 1 mRNAPC1 mRNATRPP1 mRNATransient receptor potential cation channel subfamily P member 1 mRNA

MicroRNA-17 inhibition to de-repress PKD1 mRNA translation and mRNA replacement to provide exogenous functional transcripts.