Magnetically guided non-invasive CRISPR-Cas9/gRNA delivery across blood-brain barrier to eradicate latent HIV-1 infection

Sci Rep. 2019 Mar 8;9(1):3928. doi: 10.1038/s41598-019-40222-4.

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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Blood-Brain Barrier / virology*
  • CRISPR-Cas Systems
  • Cells, Cultured
  • Drug Delivery Systems
  • Gene Editing / methods
  • HIV Infections / therapy*
  • HIV Infections / virology*
  • HIV-1* / genetics
  • Humans
  • In Vitro Techniques
  • Magnetite Nanoparticles / administration & dosage
  • RNA, Guide, CRISPR-Cas Systems / administration & dosage*
  • RNA, Guide, CRISPR-Cas Systems / genetics
  • Virus Latency

Substances

  • Magnetite Nanoparticles
  • RNA, Guide, CRISPR-Cas Systems