Ebrahimi Sasha B, Bhattacharjee Himanshu, Sonti Sujatha, Fuerst Doug, Doyle Patrick S, Lu Yi, Samanta Devleena
Emerging Drug Delivery Platforms, GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA, USA.
Drug Product Development, GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA, USA.
Nat Chem Eng. 2024 Dec;1(12):741-750. doi: 10.1038/s44286-024-00152-z. Epub 2024 Dec 23.
Oligonucleotide therapeutics are revolutionizing disease treatment by regulating molecules at the genetic level, offering the possibility of treating conditions that were once considered "undruggable." However, delivering oligonucleotides to tissues beyond the liver remains a key challenge, limiting their clinical applications thus far to niche indications. To achieve broader applicability, extensive biomolecular engineering is necessary to enhance the stability, tissue targetability, pharmacokinetics, and pharmacodynamics of these structures. The intricate design of these molecules also demands sophisticated process engineering techniques. Herein, we provide a collaborative from academia and industry on the pivotal role of chemical engineering in expanding the use of therapeutic oligonucleotides to treat a wider range of diseases. We discuss how the interplay between biomolecular and process engineering impacts the developability of next-generation oligonucleotide therapeutics as well as their translation from bench to bedside.
寡核苷酸疗法正在通过在基因水平上调节分子来彻底改变疾病治疗方式，为治疗曾经被认为“不可成药”的病症提供了可能性。然而，将寡核苷酸递送至肝脏以外的组织仍然是一个关键挑战，这限制了它们目前仅在特定适应症中的临床应用。为了实现更广泛的适用性，需要进行大量的生物分子工程来增强这些结构的稳定性、组织靶向性、药代动力学和药效学。这些分子的复杂设计也需要复杂的工艺工程技术。在此，我们提供了一篇来自学术界和工业界的合作文章，阐述了化学工程在扩大治疗性寡核苷酸用于治疗更广泛疾病方面的关键作用。我们讨论了生物分子工程与工艺工程之间的相互作用如何影响下一代寡核苷酸疗法的可开发性以及它们从实验室到临床的转化。
