PRIME Objectives

Our objectives and how we will measure success.
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MILLION IMPACTED
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INNOVATIVE OBJECTIVES
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SPECIALIST RESEARCHERS
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EUROPEAN PARTNERS

01

Developing molecular communication simulation and modeling design tool.

Objective one includes:

  1. Simulating end-to-end molecular communication of molecules (e.g., tsRNA) diffusion through the device, intracellular signaling for logic computing, and release of GDNF
  2. Use of AI to design molecular logic gates using circuit theory and device structural design (optimized volume and scaffold dimensions).

Measure of success

In silico effectiveness of the bio-computing circuit for timely production of GDNF.

Objective two includes:

  1. Defining the molecular pathway to sense and suppress seizures
  2. Design and validation of pathway whereby tsRNA build- up in advance of a seizure competes with a GDNF-blocking miRNA, thereby prompting translation and release of GDNF
  3. Fail-safe pathway that securely triggers GDNF from a preformed releasable pool in response to seizure-induced rise in intracellular calcium concentrations.

Measure of success

Complete sense-and-release of seizure-suppressant molecule.

02

Engineering cells to sense, perform logic computing and release GDN

03

Developing an encapsulated implantable device that integrates three-dimensional (3D) constructs of the cells from Objective 2 grown in hybrid biomaterial scaffolds.

Objective three includes:

  1. Development of porous Polydimethylsiloxane (PDMS) membrane dimensioned and surface-treated to enable tsRNAs and GDNF diffusion
  2. Development of biocompatible hybrid microenvironment, i.e. comprised of hydrogel and electrospun non- woven porous nanofibers from brain natural polymers
  3. Create a viable environment for the development of 3D constructs of engineered cells grown in the hybrid scaffolds.
  4. Integrate 1-3 into a functional biocompatible bio-computing circuit that will be tested in vitro.

Measure of success

Diffusion effectiveness of molecules through the membrane and scaffold for engineered ARPE cells to receive and releasing GDNF molecules

Objective four includes:

  1. in vivo validation of the device for responsiveness to changes in tsRNA fragments
  2. in vivo evaluation of the implant performance in two rodents models of epilepsy
  3. post-explant evaluation of implant function and tracking of epilepsy phenotype

Measure of success

Preclinical evidence for the effectiveness of the device to reduce or fully- prevent seizures in a models of drug-resistant epilepsy.

04

Experimental testing and validation of device in vivo.