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This activated protein and nucleic acid complex can then elicit gene silencing by binding, through perfect complementarity, to a single target m RNA sequence, thereby targeting it for cleavage and degradation.
si RNA must be transfected into cells either by cationic lipid or polymer-based transfection reagents, electroporation (physical delivery via plasma membrane holes created by an electrical field), or adding chemical modifications to the duplex to aid in uptake by the cell.
Early work on si RNA design established conventional guidelines for si RNA structural attributes that led to reasonable functional knockdown in specific cases .
The properties of potent si RNAs were further refined by performing large-scale functional studies that defined thermodynamic and sequence-based rules for rational si RNA design .
Despite progress in systemic small interfering RNA (si RNA) delivery to the liver and to solid tumors, systemic si RNA delivery to leukocytes remains challenging.
The ability to silence gene expression in leukocytes has great potential for identifying drug targets and for RNAi-based therapy for leukocyte diseases.
Small double-strand si RNAs are transfected into cells where the guide strand is loaded into RISC.si RNAs can also be used for knockdown of non-protein coding genes, such as long noncoding RNAs (lnc RNA). The antisense strand is a perfect reverse complement of the intended target m RNA.si RNAs consist of two RNA strands, an antisense (or guide) strand and a sense (or passenger) strand, which form a duplex 19 to 25 bp in length with 3' dinucleotide overhangs (Figure 1).Finally, the strategy of pooling several independent si RNAs that target an individual gene has been shown to reduce the total number of non-specific gene targets and the frequency of off-target phenotypes while preserving potent target gene knockdown .All of these strategies, when combined, work efficiently to reduce off-targeting and to achieve potent and specific silencing for a successful RNAi experiment.
Here, we designed lipidbased nanoparticles (LNPs) coated with anti-CD38 monoclonal antibodies that are specifically taken up by human MCL cells in the bone marrow of xenografted mice.