Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury

Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.

Macrophage membrane-coated nanocarriers Co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer's disease mice

Neuronal mitochondrial dysfunction caused by excessive reactive oxygen species(ROS)is an early event of sporadic Alzheimer's disease(AD),and considered to be a key pathologic factor in the progression of AD.The targeted delivery of the antioxidants to mitochondria of injured neurons in brain is a promising therapeutic strategy for AD.A safe and effective drug delivery system(DDS)which is able to cross the blood-brain barrier(BBB)and target neuronal mitochondria is necessary.Recently,bioactive materials-based DDS has been widely investigated for the treatment of AD.Herein,we developed macrophage(MA)membrane-coated solid lipid nanoparticles(SLNs)by attaching rabies virus glycoprotein(RVG29)and triphenylphosphine cation(TPP)molecules to the surface of MA membrane(RVG/TPP-MASLNs)for functional antioxidant delivery to neuronal mitochondria.According to the results,MA membranes camouflaged the SLNs from being eliminated by RESrich organs by inheriting the immunological characteristics of macrophages.The unique properties of the DDS after decoration with RVG29 on the surface was demonstrated by the ability to cross the BBB and the selective targeting to neurons.After entering the neurons in CNS,TPP further lead the DDS to mitochondria driven by electric charge.The Genistein(GS)-encapsulated DDS(RVG/TPP-MASLNs-GS)exhibited the most favorable effects on reliveing AD symptoms in vitro and in vivo by the synergies gained from the combination of MA membranes,RVG29 and TPP.These results demonstrated a promising therapeutic candidate for delaying the progression of AD via neuronal mitochondria-targeted delivery by the designed biomimetic nanosystems.

Corrigendum to“Macrophage membrane-coated nanocarriers Co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer’s disease mice”[Bioactive materials 6(2021)529-542]

The authors regret publishing the incorrect address and affiliation.They have been now revised as follows:1.The Addresses are updated from.“a School of Traditional Chinese Medicine,Shenyang Pharmaceutical University,Shenyang,110016,PR China b State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Institute of Pharmacology and Toxicology,Beijing,100850,PR China c School of Functional Food and Wine,Shenyang Pharmaceutical University,Shenyang,10016,PR China.