Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA.
Chem Soc Rev. 2012 Apr 7;41(7):2696-706. doi: 10.1039/c2cs15303c. Epub 2012 Feb 17.
Advances in recombinant techniques have led to the development of genetically engineered polymers with exquisite control over monomer sequence and polymer length. The ability to study how precise structures correlate with function has provided opportunities for the utility of these polymers in drug delivery. Chemically derived and developed methods of synthesis have yielded many useful polymers for drug delivery to-date, including those currently used in patients. However they have drawbacks, including limitations involved in statistical characterization of conventional polymer synthetic techniques. Encoding at the genetic level and production of such recombinant polymers in organisms allow for precise order and accuracy of amino acid residues and production of monodisperse polymers with specific function and physicochemical properties. Research into elastin-like, silk-like, and silk-elastinlike protein polymers for example has led to the development of delivery systems based on natural motifs of structural proteins to take advantage of their physicochemical properties. Additionally, protein based polymers on other natural motifs and de novo designs are starting to produce promising constructs for drug and gene delivery applications where precise control over structure promises correlation with function and guides the development of new and improved constructs. Clinical applications based on recombinant polymers for delivery of bioactive agents have not been realized at this point. However lessons learned from fundamental research with these polymers can be used to guide design of safe and effective systems for use in the clinic. This tutorial review summarizes progress made in the design and utility of recombinant polymers in drug and gene delivery and discusses challenges and future directions of such polymers for this purpose.
重组技术的进步导致了具有精细控制单体序列和聚合物长度的基因工程聚合物的发展。能够研究精确结构如何与功能相关联，为这些聚合物在药物输送中的应用提供了机会。迄今为止，化学衍生和开发的合成方法已经产生了许多用于药物输送的有用聚合物，包括目前在患者中使用的那些。然而，它们存在一些缺点，包括常规聚合物合成技术在统计特性方面的限制。在遗传水平上进行编码和在生物体中生产此类重组聚合物，可以实现氨基酸残基的精确顺序和准确性，并生产具有特定功能和物理化学性质的单分散聚合物。例如，对弹性蛋白样、丝蛋白样和丝弹性蛋白样蛋白聚合物的研究导致了基于结构蛋白天然基序的输送系统的开发，以利用其物理化学性质。此外，基于其他天然基序和从头设计的蛋白质聚合物开始产生用于药物和基因输送应用的有前途的构建体，其中对结构的精确控制与功能相关联，并指导新的和改进的构建体的开发。基于重组聚合物用于生物活性剂输送的临床应用尚未实现。然而，从这些聚合物的基础研究中吸取的经验教训可以用于指导安全有效的系统设计，以便在临床上使用。本教程综述总结了在药物和基因输送中设计和使用重组聚合物方面取得的进展，并讨论了此类聚合物在这方面的挑战和未来方向。
