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Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics

Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics

Published on: July 16, 2018

Tunable protease-activatable virus nanonodes.

Justin Judd¹, Michelle L Ho, Abhinav Tiwari

¹Department of Bioengineering and ‡Department of Biochemistry and Cell Biology, Rice University , Houston, Texas 77005, United States.

|May 7, 2014

Summary

This summary is machine-generated.

Engineered adeno-associated viruses (AAV) act as signal-integrating nodes. These protease-activatable viruses (PAVs) can be programmed to require multiple protease signals for gene delivery activation, enabling digital logic functions.

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Surface Functionalization of Hepatitis E Virus Nanoparticles Using Chemical Conjugation Methods

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Published on: May 11, 2018

Area of Science:

Biotechnology
Molecular Biology
Nanotechnology

Background:

Adeno-associated virus (AAV) is a clinically validated vector for human gene therapy.
AAV's self-assembling protein capsid possesses unique signal integration capabilities.
Current gene delivery systems require enhanced control over vector activation.

Purpose of the Study:

To engineer AAV capsids for proteolytic regulation of infection.
To investigate the signal integration properties of engineered protease-activatable viruses (PAVs).
To demonstrate the potential for viruses to function as digital logic gates for gene delivery.

Main Methods:

Engineering AAV capsids for protease-dependent activation.
Characterizing the nonlinear transfer function of PAVs relating proteolysis to activity.
Constructing mosaic PAVs utilizing dynamic polyvalency and self-assembly for AND gate logic.

Main Results:

Engineered PAVs exhibit a highly nonlinear transfer function, indicating complex signal processing.
Dynamic polyvalency contributes to the nonlinear response of PAVs.
Mosaic PAVs successfully operated under a digital AND gate regime, requiring dual protease inputs for activation.

Conclusions:

Viruses can be engineered as sophisticated signal-integrating nanoscale nodes.
PAVs' functional properties can be precisely regulated by multiple proteolytic signals.
This represents a promising advancement for the precise control of gene delivery systems.