Haematological Malignancies and Nucleic Acid Therapeutics

1537 Words4 Pages

It’s Not Just a Nucleic Acid - Aptamer conjugates,Systemic delivery would be advantageous and provide more clinical appeal, in spite of the above mentioned limitations, and it is now becoming more common to link the RNAi to compounds, such as ligands or peptides to achieve target specificity and nuclease resistance, thereby eliminating some of the non-targeted effects (Bhindi et al 2007). Aptamers represent a unique alternative in the ability to specifically target cancer cells. Aptamers have been developed that target both extracellular protein ligands, as well as intracellular proteins. Those that target the extracellular domains of transmembrane receptor proteins can facilitate the entry of RNAi into cells via receptor mediated endocytosis (Fig 2(ii)) (Vorhies & Nemunaitis 2007, Syed & Pervaiz 2010). What makes aptamers such a perfect therapeutic is the difference between these and other nucleic acid therapeutics. Aptamers, by themselves, are not necessarily effective therapeutics per se. They can block their target function, and, if internalising aptamers are selected, they can prove to be much more effective as therapeutics through the direct conjugation of drugs or attaching nanoparticles as drug delivery devices. The choice of a suitable therapeutic target is governed by the need to target cancerous cells while leaving healthy cells intact. This is where both aptamers and RNAi come into their element. RNAi can be used to target disease-specific sequences within the cell, while the aptamer can guide the RNAi to the abnormal cell, thus minimising off-target effects. This also has benefits when considering the ability of RNAi to target the T3151 point mutation in Abl which promotes imatinib-resistance. Through the use of gene ...

... middle of paper ...

... and has recently awarded another $1.6 million to research the role of miRNAs in cancer, indicating this is a field of increasing research priority and relevance. Given the success of directed targeting with aptamers, and the success of non-targeting RNAi and ASOs, it is now time to start combining these nucleic acid therapeutics to achieve a more effective treatment. The problem of off-target effects can be circumnavigated by hiding non-specific nucleic acids inside nanoparticles which can be degraded once inside the cell to release their contents, or directly conjugating these to aptamers to reduce the off-target effects. Specific targeting will mean that nucleic acids that don’t specifically target a pathway related to malignancy, or that had severe off-target effects, can now get a second chance as therapeutic treatments. It may just take that one small step.,.

More about Haematological Malignancies and Nucleic Acid Therapeutics

Open Document