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01 21, 2025;19 (2): 1865-1883.

Autonomous Nucleic Acid and Protein Nanocomputing Agents Engineered to Operate in Living Cells.

Martin Panigaj, Tanaya Basu Roy, Elizabeth Skelly, Morgan R Chandler, Jian Wang, Srinivasan Ekambaram, Kristin Bircsak, Nikolay V Dokholyan, Kirill A Afonin
Author Information
  1. Martin Panigaj: Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, United States.
  2. Tanaya Basu Roy: Department of Pharmacology, Department of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
  3. Elizabeth Skelly: Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, United States.
  4. Morgan R Chandler: MIMETAS US, INC, Gaithersburg, Maryland 20878, United States. ORCID
  5. Jian Wang: Department of Pharmacology, Department of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
  6. Srinivasan Ekambaram: Department of Pharmacology, Department of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
  7. Kristin Bircsak: MIMETAS US, INC, Gaithersburg, Maryland 20878, United States.
  8. Nikolay V Dokholyan: Department of Pharmacology, Department of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States. ORCID
  9. Kirill A Afonin: Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, United States. ORCID
PMID: 39760461 DOI: 10.1021/acsnano.4c13663

Abstract

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.

Keywords

directed evolution nanocomputing agents nucleic acid nanoparticles proteins rational design

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Grants

  1. R35 GM134864/NIGMS NIH HHS
  2. R35 GM139587/NIGMS NIH HHS

MeSH Term

Nucleic Acids
Humans
Proteins
Protein Engineering
Nanotechnology

Chemicals

Nucleic Acids
Proteins
Journal Article Review Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't
Article has an altmetric score of 2

Word Cloud

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