Department of Biochemistry, Albert Einstein College of Medicine , Bronx, New York.
Nucleic Acid Ther. 2018 Jun;28(3):194-199. doi: 10.1089/nat.2018.0732.
Targeting cells with aptamers for the delivery of therapeutic cargoes, in particular oligonucleotides, represents one of the most exciting applications of the aptamer field. Perhaps nowhere has there been more excitement in the field than around the targeted delivery of siRNA or miRNA. However, when industry leaders in the field of siRNA delivery have tried to recapitulate aptamer-siRNA delivery results, they have failed. This problem stems from more than just the age-old problem of delivery to the cytoplasm, a challenge that has stymied the targeted delivery of therapeutic oligonucleotides since its inception. With aptamers, the problem is compounded further by the fact that many aptamers simply do not function as reported. This is distressing, as clearly, all published aptamers should be able to function as described. However, it is often challenging to recognize the details that might flag an unreliable aptamer from a viable one. As such, unreliable aptamers continue to be peer reviewed and published. We need to raise the bar and level of rigor in the field. Only then can we think about taking advantage of the unique attributes of these molecules and address the issues associated with their use as agents for targeted delivery.
利用适体靶向细胞递送治疗性货物，特别是寡核苷酸，是适体领域最令人兴奋的应用之一。在靶向递送 siRNA 或 miRNA 方面，该领域可能比其他任何领域都更令人兴奋。然而，当 siRNA 递送领域的行业领导者试图重现适体-siRNA 递送的结果时，他们失败了。这个问题不仅仅源于将治疗性寡核苷酸递送到细胞质这一由来已久的挑战，自该领域创立以来，这一挑战一直阻碍着治疗性寡核苷酸的靶向递送。对于适体来说，问题更加复杂，因为许多适体根本无法像报道的那样发挥作用。这令人痛心，因为显然，所有已发表的适体都应该能够按照描述发挥作用。然而，从可行的适体中识别可能标志着不可靠适体的细节往往具有挑战性。因此，不可靠的适体仍在被同行评审和发表。我们需要提高该领域的标准和严谨性。只有这样，我们才能考虑利用这些分子的独特属性，并解决与将其用作靶向递送剂相关的问题。
