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Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
Published on: July 23, 2016
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Targeted cellular micropharmacies deliver therapeutic agents to the brain
Manish Malviya1,2, Subha Baniya1,3, Eitan Wong4
1Molecular Pharmacology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
EMBO Molecular Medicine
|April 14, 2026
Summary
Genetically engineered T-cells act as brain drug delivery systems, targeting Alzheimer's disease by blocking CD33 to enhance amyloid plaque clearance. This cellular micropharmacy approach offers sustained therapeutic protein delivery for neurological disorders.
Area of Science:
- Neuroscience
- Immunology
- Biotechnology
Background:
- Systemic drug delivery to the central nervous system (CNS) is challenging for large molecules like antibodies, limiting treatment efficacy for CNS disorders.
- Neurodegenerative diseases necessitate long-term treatment strategies, making repeated intrathecal injections impractical.
- Alzheimer's disease (AD) pathology involves amyloid-beta (Aβ) plaques, with microglia playing a role in Aβ clearance, but their function is inhibited by CD33.
Purpose of the Study:
- To develop a novel cellular platform for targeted therapeutic protein delivery directly into the brain.
- To engineer CD4 T-cells as "targeted cellular micropharmacies" for sustained CNS drug delivery.
- To investigate the potential of blocking CD33 to enhance microglial phagocytosis of Aβ and slow AD progression.
Main Methods:
- Genetically engineered CD4 T-cells to express a GD2 chimeric antigen receptor for brain retention.
- Incorporated ectopic FoxP3 expression to modulate immune responses and reduce inflammation.
- Engineered T-cells to secrete Interleukin-2 (IL-2) for enhanced cell longevity and an anti-CD33 single-chain variable fragment (scFv) antibody for therapeutic targeting.
Main Results:
- Demonstrated proof-of-concept for cellular micropharmacies retaining therapeutic antibodies in the CNS.
- Achieved sustained delivery of therapeutic antibodies to the brain for a minimum of 8 weeks.
- Validated the potential of engineered T-cells to deliver therapeutic agents for neurological disorders.
Conclusions:
- Genetically engineered T-cells can serve as effective cellular micropharmacies for sustained therapeutic delivery to the brain.
- This platform offers a promising alternative to conventional drug delivery methods for treating CNS disorders like Alzheimer's disease.
- The approach is adaptable for delivering various therapeutic agents beyond antibodies for neurological conditions.
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