L2-siRNA

L2-siRNA is a chemically defined lipid–siRNA conjugate platform designed to enhance gene silencing efficacy within the central nervous system (CNS)[1][2]. It consists of small interfering RNA (siRNA) duplexes with alternating 2'-O-methyl and 2'-fluoro modifications, phosphorothioate linkages at strand ends, and a vinyl phosphonate at the 5’ antisense position for stability and activity[1]. The defining feature is its branch from the 5’ sense strand containing an 18-ethylene glycol spacer and two 18-carbon stearyl lipid tails, which promote albumin binding and perivascular transport in cerebrospinal fluid[1][2][3]. This conjugation increases tissue penetration and cell uptake compared to unconjugated siRNA, without causing the toxicity associated with cationic nanocarriers[1][3]. L2-siRNA is specifically optimized for CNS delivery via intrathecal and intracerebroventricular routes, targeting gene silencing across diverse brain cell types for potential treatment of neurodegenerative and CNS disorders[2][1]. The platform's mechanism is RNA interference: the antisense siRNA strand directs the RNA-induced silencing complex (RISC) to degrade specific target mRNA, thus reducing expression of the target gene[1][2][3].

Other names

L2-siRNAL-2-siRNAL 2-siRNAsiRNA-L2siRNA-L-2siRNA-L 2