Study Published in Alzheimer’s & Dementia by Konofagou and Leong Labs Explores FUS-Mediated Delivery of Gene Editing Tools Targeting APOE ε4

A collaboration between the laboratories of Dr. Elisa E. Konofagou (Biomedical Engineering & Radiology) and Dr. Kam W. Leong (Biomedical Engineering) at Columbia University has been published in Alzheimer’s & Dementia (DOI: 10.1002/alz.70464). The paper explores the use of focused ultrasound (FUS) to transiently open the blood–brain barrier, enabling systemic delivery of adeno-associated virus (AAV) vectors carrying CRISPR gene editing components to knock down human APOE ε4 in a humanized mouse model.

Title: Focused ultrasound-mediated APOE4 knockdown in mouse brain

Authors: Kaiyuan Zheng, Fotios N. Tsitsos, Alec J. Batts, Robin Ji, Tal Nuriel, Elisa E. Konofagou, Kam W. Leong

Key findings include:

  • FUS-mediated opening of the blood–brain barrier effectively localized AAV–CRISPR delivery to targeted brain regions.
  • APOE ε4 protein expression was significantly reduced following treatment.

  • Decreases in markers of astrocyte and microglial activation were observed.

     

Given that APOE ε4 is a major genetic risk factor for late-onset Alzheimer’s disease, this study provides a methodical evaluation of a noninvasive, targeted platform for gene-editing delivery to the brain.

For full details, please refer to the original publication in Alzheimer’s & Dementia (DOI: 10.1002/alz.70464) or contact the Konofagou or Leong laboratories.

July 16, 2025