Adeno-Associated Virus-Mediated Immunotherapy Based on Bispecific Tandem scFv for Alzheimer's Disease.
J Alzheimers Dis
; 93(2): 435-448, 2023.
Article
en En
| MEDLINE
| ID: mdl-37038816
ABSTRACT
BACKGROUND:
Patients with Alzheimer's disease (AD) have considerably increased globally as a result of population aging, placing a significant burden on the global economy and the medical system. The outcome of clinical trials for AD immunotherapy that solely targeted amyloid-ß (Aß) or phosphorylated tau protein (p-Tau) was unsatisfactory. Therefore, blocking both Aß and p-Tau's pathological processes simultaneously while also preventing their interaction may be the key to developing an effective AD therapy.OBJECTIVE:
To develop a novel immunotherapy based on bispecific tandem scFv (TaFv) against AD.METHODS:
Bispecific single-chain antibody that targets both Aß and p-Tau were obtained using E. coli expression system. Biological ability of TaFvs were determined by ELISA, SDS-PAGE, and immunohistochemical assay. Recombinant adeno-associated virus 9 (rAAV9) were packaged to create TaFv. The in vivo activity of rAAV9 were detected in mouse, using biophotonic imaging and frozen section methods.RESULTS:
The outcomes demonstrated that both Aß and p-Tau had a high affinity for the bispecific TaFv. Additionally, it can bind to the amyloid plaques and neuronal tangles in the brain slices of an AD mouse model. Moreover, the rAAV9 could infect neuronal cells, transverse the blood-brain barrier, and express TaFv in the mouse brain.CONCLUSION:
This novel immunotherapy offers a fresh concept for the immunotherapy of AD and successfully delivers the double target antibody into the brain, acting on both pathogenic substances Aß and p-Tau.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Anticuerpos Biespecíficos
/
Enfermedad de Alzheimer
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China