Alejandro Da Silva Sanchez

Member for

1 year 11 months
First Name
Last Name
Da Silva Sanchez
Studying for
Thesis Project Title
The impact of the metabolic state of a cell on nucleic acid therapeutics
Thesis Project Description

Nucleic acid therapies have advanced over the last decade with the FDA approval of the first  siRNA drug in 2018 and the recent approval of COVID vaccines leveraging mRNA technology.  While surface receptors and endocytosis genes have been shown to influence the effectiveness  of RNA drug delivery with lipid nanoparticles (LNPs), the effect of the metabolic state of a cell  upon therapies seeking to produce or silence proteins remains understudied. This project  therefore aims to (i) understand whether metabolic perturbations to the mTOR pathway upon  PIP3 extracellular administration affect LNP-mediated mRNA delivery, (ii) develop cell- and  mouse-agnostic high throughput LNP screening systems for siRNA and DNA drugs that will allow  scientists to perform mechanistic studies on functional delivery with genetic knockout mice, and  (iii) leverage these platforms to study whether mice exhibiting different levels of activity across  the mTOR signaling pathway are more or less receptive to different nucleic acid drugs. This work  will constitute early steps toward two equally important goals: (a) exploiting natural differences in  cell signaling to improve cell type–specific nanoparticle delivery and (b) understanding how  different physiological states can lead to different delivery potencies of nucleic acid therapeutics.

Research Areas
Pharmaceuticals & Drug Delivery