Investigating the In Vivo Effects of Anti-Prion Protein Nanobodies on Prion Disease with AAV Vector DOI Creative Commons
Jingjing Zhang, Mengfei Wang, Dan Wang

et al.

Pathogens, Journal Year: 2025, Volume and Issue: 14(2), P. 131 - 131

Published: Feb. 2, 2025

Prion diseases are fatal neurodegenerative disorders affecting humans and animals, the central pathogenic event is conversion of normal prion protein (PrPC) into PrPSc isoform. Previous studies have identified nanobodies that specifically recognize PrPC inhibit to in vitro. In this study, we investigated potential for vivo expression anti-PrPC evaluated their impact on disease. The coding sequences three were packaged recombinant adeno-associated virus (rAAV) administered via intracerebroventricular (ICV) injection newborn mice. We found these remained robust over 180 days, with no observed detrimental effects. To assess therapeutic potential, performed ICV injections nanobody-expressing rAAVs mice, followed by intracerebral inoculation at 5–6 weeks age. One nanobody exhibited a small yet statistically significant effect, extending survival time from 176 days 184 days. Analyses diseased brains revealed did not alter pathological changes. Our findings suggest high levels necessary delay disease progression. Further optimization nanobodies, AAV vectors, or delivery methods essential achieve effect.

Language: Английский

Base editing reduces prion protein DOI
Sarah Crunkhorn

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: 24(3), P. 169 - 169

Published: Jan. 22, 2025

Language: Английский

Citations

0
Investigating the In Vivo Effects of Anti-Prion Protein Nanobodies on Prion Disease with AAV Vector DOI Creative Commons
Jingjing Zhang, Mengfei Wang, Dan Wang

et al.

Pathogens, Journal Year: 2025, Volume and Issue: 14(2), P. 131 - 131

Published: Feb. 2, 2025

Prion diseases are fatal neurodegenerative disorders affecting humans and animals, the central pathogenic event is conversion of normal prion protein (PrPC) into PrPSc isoform. Previous studies have identified nanobodies that specifically recognize PrPC inhibit to in vitro. In this study, we investigated potential for vivo expression anti-PrPC evaluated their impact on disease. The coding sequences three were packaged recombinant adeno-associated virus (rAAV) administered via intracerebroventricular (ICV) injection newborn mice. We found these remained robust over 180 days, with no observed detrimental effects. To assess therapeutic potential, performed ICV injections nanobody-expressing rAAVs mice, followed by intracerebral inoculation at 5–6 weeks age. One nanobody exhibited a small yet statistically significant effect, extending survival time from 176 days 184 days. Analyses diseased brains revealed did not alter pathological changes. Our findings suggest high levels necessary delay disease progression. Further optimization nanobodies, AAV vectors, or delivery methods essential achieve effect.

Language: Английский

Citations

0