It's not just about nucleic acid - aptamer conjugates, systemic administration would be advantageous and offer more clinical appeal, despite the limitations mentioned above, and it is increasingly common to link RNAi to compounds, such as ligands or peptides, to achieve target specificity and nuclease resistance, thereby eliminating some of the off-target effects (Bhindi et al 2007). Aptamers represent a unique alternative in their ability to specifically target cancer cells. Aptamers have been developed to target both extracellular protein ligands and intracellular proteins. Those that target the extracellular domains of transmembrane receptor proteins can facilitate RNAi entry into cells via receptor-mediated endocytosis (Fig 2(ii)) (Vorhies & Nemunaitis 2007, Syed & Pervaiz 2010). What makes aptamers such a perfect therapeutic product is the difference between them and other nucleic acid therapeutics. Aptamers, by themselves, are not necessarily effective therapeutic agents in their own right. They can block their target function and, if internalizing aptamers are selected, they may prove much more effective as therapeutic agents through direct drug conjugation or attachment of nanoparticles as drug delivery devices. The choice of a suitable therapeutic target is governed by the need to target cancer cells while leaving healthy cells intact. This is where aptamers and RNAi come into their element. RNAi can be used to target disease-specific sequences in the cell, while the aptamer can guide the RNAi to the abnormal cell, thereby minimizing off-target effects. This also has advantages when considering the ability of RNAi to target the T3151 point mutation in Abl, which promotes resistance to imatinib. Through the use of the gene...... middle of article...... and recently awarded an additional $1.6 million for research into the role of miRNAs in cancer, indicating that this is a priority and relevant area of ​​research. Given the success of directed targeting with aptamers and the success of untargeted RNAi and ASO, now is the time to start combining these nucleic acid-based therapies to achieve more effective treatment. The problem of off-target effects can be circumvented by hiding non-specific nucleic acids in nanoparticles that can be degraded once inside the cell to release their contents, or by conjugating them directly to aptamers to reduce off-target effects. target. Specific targeting will mean that nucleic acids that do not specifically target a malignancy-related pathway, or that have had serious off-target effects, may now be given a second chance as therapeutic treatments. It may just be a small step.,.