Invention Title:

EVOLUTION OF FLUOROGENIC SENSORS

Publication number:

US20260139001

Publication date:

2026-05-21

Section:

Chemistry; metallurgy

Class:

C07H21/02

Inventors:

James J. Collins 🇺🇸 Newton, MA, United States

Helena de Puig Guixe 🇺🇸 Cambridge, MA, United States

George M. Church 🇺🇸 Cambridge, MA, United States

Jonathan Rittichier 🇺🇸 Cambridge, MA, United States

Daniel J. Wiegand 🇺🇸 Cambridge, MA, United States

Erkin Kuru 🇺🇸 Cambridge, MA, United States

Isaac Han 🇺🇸 Cambridge, MA, United States

Subhrajit Rout 🇺🇸 Cambridge, MA, United States

Assignees:

President and Fellows of Harvard College 🇺🇸 Cambridge, MA, United States

MASSACHUSETTS INSTITUTE OF TECHNOLOGY 🇺🇸 Cambridge, MA, United States

Applicants:

Massachusetts Institute of Technology 🇺🇸 Cambridge, MA, United States

PRESIDENT AND FELLOWS OF HARVARD COLLEGE 🇺🇸 Cambridge, MA, United States

Smart overview of the Invention

The development of fluorogenic sensors involves an evolution strategy that utilizes efficient tRNA charging chemistry for cell-free ribosomal translation of proteins. These sensors are designed to detect various targets, including antigens like SARS-CoV-2 variants, such as Omicron. The innovation aims to improve biosensors by overcoming challenges related to low-throughput and inefficient probe coupling methods.

Fluorogenic Molecules and Protein Binding

Fluorogenic molecules are conditionally fluorescent, meaning they can change their fluorescence properties in response to specific chemical or physical events. Such changes often occur at protein-protein binding interfaces, such as those between proteins and antigens. By conjugating fluorogenic molecules to antigen-binding proteins, these sensors can detect binding events with low background fluorescence.

Platform for Biosensor Development

The described platform facilitates the preparation and utilization of fluorogenic sensors through a novel evolution strategy. This approach accelerates the molecular design of biosensors, making them applicable in diagnostics, bio-surveillance, and molecular imaging. Improved methods for acylating nucleotides with non-standard amino acids are also provided, enhancing the synthesis of these sensors.

Methods of Acylation and Sensor Sensitivity

The patent outlines methods for selectively acylating nucleotides, such as pdCpA, at specific positions using acylimidazole in a water-based solvent. These methods enable the production of fluorogenic sensors with increased sensitivity, particularly for detecting SARS-CoV-2 variants and other targets like EGFR proteins, cortisol, and ALFA protein.

Applications and Detection Methods

The fluorogenic sensors are capable of detecting specific targets by binding to them, which alters the fluorescence of the sensor. This technology can be used to identify the presence of various targets, including SARS-CoV-2 variants and proteins like EGFR. The sensors are based on specific sequences and are optimized for sensitivity and specificity, providing valuable tools for research and disease management.