Magnetically guided non-invasive CRISPR-Cas9/gRNA delivery across blood-brain barrier to eradicate latent HIV-1 infection.
Sci Rep
; 9(1): 3928, 2019 03 08.
Article
in En
| MEDLINE
| ID: mdl-30850620
ABSTRACT
CRISPR-Cas9/gRNA exhibits therapeutic efficacy against latent human immunodeficiency virus (HIV) genome but the delivery of this therapeutic cargo to the brain remains as a challenge. In this research, for the first time, we demonstrated magnetically guided non-invasive delivery of a nano-formulation (NF), composed of Cas9/gRNA bound with magneto-electric nanoparticles (MENPs), across the blood-brain barrier (BBB) to inhibit latent HIV-1 infection in microglial (hµglia)/HIV (HC69) cells. An optimized ac-magnetic field of 60 Oe was applied on NF to release Cas9/gRNA from MENPs surface and to facilitate NF cell uptake resulting in intracellular release and inhibition of HIV. The outcomes suggested that developed NF reduced HIV-LTR expression significantly in comparison to unbound Cas9/gRNA in HIV latent hµglia/HIV (HC69) cells. These findings were also validated qualitatively using fluorescence microscopy to assess NF efficacy against latent HIV in the microglia cells. We believe that CNS delivery of NF (CRISPR/Cas9-gRNA-MENPs) across the BBB certainly will have clinical utility as future personalized nanomedicine to manage neuroHIV/AIDS.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood-Brain Barrier
/
HIV Infections
/
HIV-1
/
RNA, Guide, Kinetoplastida
Type of study:
Evaluation_studies
Aspects:
Implementation_research
Limits:
Humans
Language:
En
Journal:
Sci Rep
Year:
2019
Document type:
Article
Affiliation country:
United States