Panigaj Martin, Basu Roy Tanaya, Skelly Elizabeth, Chandler Morgan R, Wang Jian, Ekambaram Srinivasan, Bircsak Kristin, Dokholyan Nikolay V, Afonin Kirill A
Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, United States.
Department of Pharmacology, Department of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
ACS Nano. 2025 Jan 21;19(2):1865-1883. doi: 10.1021/acsnano.4c13663. Epub 2025 Jan 6.
In recent years, the rapid development and employment of autonomous technology have been observed in many areas of human activity. Autonomous technology can readily adjust its function to environmental conditions and enable an efficient operation without human control. While applying the same concept to designing advanced biomolecular therapies would revolutionize nanomedicine, the design approaches to engineering biological nanocomputing agents for predefined operations within living cells remain a challenge. Autonomous nanocomputing agents made of nucleic acids and proteins are an appealing idea, and two decades of research has shown that the engineered agents act under real physical and biochemical constraints in a logical manner. Throughout all domains of life, nucleic acids and proteins perform a variety of vital functions, where the sequence-defined structures of these biopolymers either operate on their own or efficiently function together. This programmability and synergy inspire massive research efforts that utilize the versatility of nucleic and amino acids to encode functions and properties that otherwise do not exist in nature. This Perspective covers the key concepts used in the design and application of nanocomputing agents and discusses potential limitations and paths forward.
近年来，在人类活动的许多领域都观察到了自主技术的快速发展和应用。自主技术能够轻松地根据环境条件调整其功能，并在无需人工控制的情况下实现高效运行。虽然将相同的概念应用于设计先进的生物分子疗法将彻底改变纳米医学，但设计能够在活细胞内进行预定义操作的生物纳米计算剂的方法仍然是一个挑战。由核酸和蛋白质制成的自主纳米计算剂是一个很有吸引力的想法，二十年的研究表明，经过工程设计的试剂在真实的物理和生化限制下以合乎逻辑的方式发挥作用。在整个生命领域，核酸和蛋白质执行各种重要功能，这些生物聚合物的序列定义结构要么独立运作，要么高效协同发挥作用。这种可编程性和协同性激发了大量的研究工作，这些研究利用核酸和氨基酸的多功能性来编码自然界中原本不存在的功能和特性。这篇综述涵盖了纳米计算剂设计和应用中使用的关键概念，并讨论了潜在的局限性和未来的发展方向。
