RNA interference (RNAi) is a natural cellular process that silences the expression of target genes in a sequence-specific way by mediating targeted mRNA degradation. One of the main challenges in RNAi research is developing an effective career-free delivery system and targeting cells in the central nervous system (CNS). Recently, lipid-conjugated systems involving fatty acids have shown promising potential as safe and effective delivery systems of oligonucleotides to CNS cells due to their hydrophobic tails and interactions with the cell's hydrophobic membrane. Therefore, in this study, we are interested in creating career-free siRNA therapeutics for potential applications in drug delivery to the CNS. Here we explore different synthetic pathways of conjugating sphingolipids containing long-carbon chains to siRNA and assess their effectiveness as career-free delivery systems. In this project, a library of sphingosine-modified siRNAs was created, and their gene-silencing effect was evaluated in both the presence and absence of a transfection carrier. siRNAs modified with one or two sphingosine moieties resulted in dose-dependent gene knockdown while demonstrating promising results for their use as carrier-free agents. The IC50 values of single-modified siRNAs ranged from 49.9 nM to 670.7 nM, whereas double-modified siRNAs had IC50 values in the range of 49.9 nM to 66.4 nM. In conclusion, sphingosine-modified siRNAs show promising results in advancing carrier-free siRNA therapeutics.