TY - JOUR
T1 - AAV-aMTD-Parkin, a therapeutic gene delivery cargo, enhances motor and cognitive functions in Parkinson's and Alzheimer's diseases
AU - Lee, Seokwon
AU - Kang, Mingu
AU - Lee, Seungwoo
AU - Yoon, Sangsun
AU - Cho, Yeonjin
AU - Min, Dongjae
AU - Ann, Daye
AU - Shin, Jisoo
AU - Paik, Young Ki
AU - Jo, Daewoong
N1 - Publisher Copyright:
© 2024
PY - 2024/10
Y1 - 2024/10
N2 - Neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease (AD), have a global prevalence and profoundly impact both motor and cognitive functions. Although adeno-associated virus (AAV)-based gene therapy has shown promise, its application for treating central nervous system (CNS) diseases faces several challenges, including effective delivery of AAV vectors across the blood-brain barrier, determining optimal dosages, and achieving targeted distribution. To address these challenges, we have developed a fusion delivery therapeutic cargo called AAV-aMTD-Parkin, which combines a hydrophobic cell-penetrating peptide sequence with the DNA sequences of AAV and Parkin. By employing this fusion delivery platform at lower dosages compared to zolgensma, we have achieved significant enhancements in cell and tissue permeability, while reducing the occurrence of common pathological protein aggregates. Consequently, motor and cognitive functions were restored in animal models of PD and AD. With its dual functionality in addressing PD and AD, AAV-aMTD-Parkin holds immense potential as a novel class of therapeutic biologics for prevalent CNS diseases.
AB - Neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease (AD), have a global prevalence and profoundly impact both motor and cognitive functions. Although adeno-associated virus (AAV)-based gene therapy has shown promise, its application for treating central nervous system (CNS) diseases faces several challenges, including effective delivery of AAV vectors across the blood-brain barrier, determining optimal dosages, and achieving targeted distribution. To address these challenges, we have developed a fusion delivery therapeutic cargo called AAV-aMTD-Parkin, which combines a hydrophobic cell-penetrating peptide sequence with the DNA sequences of AAV and Parkin. By employing this fusion delivery platform at lower dosages compared to zolgensma, we have achieved significant enhancements in cell and tissue permeability, while reducing the occurrence of common pathological protein aggregates. Consequently, motor and cognitive functions were restored in animal models of PD and AD. With its dual functionality in addressing PD and AD, AAV-aMTD-Parkin holds immense potential as a novel class of therapeutic biologics for prevalent CNS diseases.
KW - Adeno-associated virus
KW - Advanced macromolecule transduction Domain
KW - Alzheimer's disease
KW - Parkinson's disease
KW - Therapeutic-molecule systemic delivery technolog
UR - http://www.scopus.com/inward/record.url?scp=85202157096&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85202157096&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2024.107326
DO - 10.1016/j.phrs.2024.107326
M3 - Article
C2 - 39069196
AN - SCOPUS:85202157096
SN - 1043-6618
VL - 208
JO - Pharmacological Research
JF - Pharmacological Research
M1 - 107326
ER -