Rational design of aptamer switches with programmable pH response

Area of Science:

• Biotechnology
• Molecular Biology
• Chemical Engineering

Background:

• Aptamers are crucial for molecular devices, but pH sensitivity has been limited.
• Previous pH-sensitive aptamers had restricted response ranges.
• Controlling aptamer function with pH is key for advanced diagnostics and therapeutics.

Purpose of the Study:

• To develop a generalizable method for creating tunable pH-sensitive aptamer switches.
• To engineer aptamers that can be controlled across acidic, neutral, and alkaline conditions.
• To enhance the efficacy of molecular devices through precise pH-based regulation.

Main Methods:

• Inserted two orthogonal motifs into aptamer sequences to enable parallel manipulation.
• Tuned pH-sensitivity without altering the core aptamer sequence.
• Engineered pH-controlled target binding using an ATP aptamer as a model.

Main Results:

• Achieved up to 1,000-fold pH-induced selectivity in aptamer binding affinity.
• Demonstrated the design of aptamers with narrow pH-specific target affinity.
• Successfully converted a standard aptamer into a versatile pH-responsive molecular switch.

Conclusions:

• The presented methodology offers a highly generalizable strategy for integrating pH-responsiveness into aptamers.
• This approach allows for the creation of molecular devices with precisely controlled pH-dependent functions.
• The engineered aptamer switches have broad applications in diagnostics and therapeutics.