Camila Aragon Alfaro

Camila Aragon Alfaro

Biography

Camila Aragón Alfaro is a rising senior at Boston University, where she studies Biomedical Engineering. Originally from Peru, Camila’s first-hand experience with healthcare disparities in underserved communities sparked her passion for research at the intersection of biology and engineering. At BU, she has worked on computational modeling of neural activity in the mouse cortex and engineering RNA-based transcriptional switches for gene regulation, and she has investigated cardiac ablation lesion biophysics at Brigham and Women’s Hospital. This summer, she is investigating the cellular uptake mechanisms of antisense oligonucleotides delivered via virus-like DNA origami particles in the Bathe Bio Nano Lab, aiming to inform the design of programmable molecular delivery systems. Her work has been featured at the 2024 BMES Annual Meeting and recognized with multiple awards, including BostonUniversity’s Harold C. Case Scholarship and Provost’s Scholars Award, as well as a national scholarship from Tau Beta Pi, the engineering honor society. Outside the lab, Camila is the president and co-founder of BU’s Peruvian club, as well as a Dean’s Host, an Engineering Ambassador, and a former Teaching Assistant. She hopes to pursue a PhD and become a professor who leads innovative research and mentors future engineers who will reimagine healthcare in underserved communities.

Abstract

Investigating the Uptake Mechanisms of ASO-Loaded Virus-Like DNA Origami

Antisense oligonucleotides (ASOs) are a powerful therapeutic platform for gene silencing, yet their clinical translation remains limited by poor cellular uptake, off-target effects, and limited nuclear delivery. DNA origami nanostructures—particularly virus-like particles (DNA-VLPs)—offer a programmable solution, enabling precise control over shape, size, and cargo presentation. While DNA origami has shown promise for enhancing ASO delivery, the use of DNA-VLPs for ASO transport remains largely unexplored, and their intracellular trafficking mechanisms uncharacterized. This project investigates how DNA-VLPs influence the uptake and functional delivery of ASOs by linking endocytic pathways to gene silencing outcomes. I will engineer DNA-VLPs carrying ASOs targeting Malat1, a nuclear long noncoding RNA, and evaluate knockdown efficiency in Neuro2a cells, a neuronal cell line, using Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR). To dissect delivery mechanisms, cells will be pre-treated with inhibitors of clathrin- and calveolae-mediated endocytosis, macropinocytosis, and scavenger receptor pathways—routes previously implicated in ASO and DNA-VLP internalization. By comparing the knockdown efficiency of free versus DNA-VLP–delivered ASOs across various perturbation conditions, this study aims to reveal which uptake routes support productive delivery. These insights will help guide the rational design of programmable delivery systems that bypass degradative pathways and improve the efficacy of ASO-based therapeutics.