Idioma:

Sonoselective transfection of cerebral vasculature without blood–brain barrier disruption

Gorick, Catherine M. ; Mathew, Alexander S. ; Garrison, William J. ; Thim, E. Andrew ; Fisher, Delaney G. ; Copeland, Caitleen A. ; Song, Ji ; Klibanov, Alexander L. ; Miller, G. Wilson ; Price, Richard J.

Proceedings of the National Academy of Sciences - PNAS, 2020-03, Vol.117 (11), p.5644-5654 [Periódico revisado por pares]

United States: National Academy of Sciences

Texto completo disponível

Citações Citado por

Enviar para

Título:
Sonoselective transfection of cerebral vasculature without blood–brain barrier disruption
Autor: Gorick, Catherine M. ; Mathew, Alexander S. ; Garrison, William J. ; Thim, E. Andrew ; Fisher, Delaney G. ; Copeland, Caitleen A. ; Song, Ji ; Klibanov, Alexander L. ; Miller, G. Wilson ; Price, Richard J.
Assuntos: Angiogenesis ; Animals ; Biological Sciences ; Blood vessels ; Blood-brain barrier ; Blood-Brain Barrier - metabolism ; Blood-Brain Barrier - radiation effects ; Disruption ; Endothelial cells ; Endothelium ; FUS gene ; Gene expression ; Gene sequencing ; Gene transfer ; Immune response ; Inflammation ; Low pressure ; Magnetic resonance imaging ; Magnetic Resonance Imaging - methods ; Male ; Medical imaging ; Mice ; Mice, Inbred C57BL ; Microbubbles ; Neural stem cells ; Physical Sciences ; Pressure ; Regrowth ; Ribonucleic acid ; RNA ; Selectivity ; Stem cells ; Transcriptome ; Transfection ; Transfection - methods ; Ultrasonic Waves ; Ultrasound
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2020-03, Vol.117 (11), p.5644-5654
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by David A. Weitz, Harvard University, Cambridge, MA, and approved February 10, 2020 (received for review August 26, 2019)
Author contributions: C.M.G., A.S.M., and R.J.P. designed research; C.M.G., A.S.M., W.J.G., E.A.T., D.G.F., C.A.C., J.S., and G.W.M. performed research; A.L.K. contributed new reagents/analytic tools; C.M.G., A.S.M., E.A.T., and R.J.P. analyzed data; and C.M.G. and R.J.P. wrote the paper.
Descrição: Treatment of many pathologies of the brain could be improved markedly by the development of noninvasive therapeutic approaches that elicit robust, endothelial cell-selective gene expression in specific brain regions that are targeted under MR image guidance. While focused ultrasound (FUS) in conjunction with gas-filled microbubbles (MBs) has emerged as a noninvasive modality for MR image-guided gene delivery to the brain, it has been used exclusively to transiently disrupt the blood–brain barrier (BBB), which may induce a sterile inflammation response. Here, we introduce an MR image-guided FUS method that elicits endothelialselective transfection of the cerebral vasculature (i.e., “sonoselective” transfection), without opening the BBB. We first determined that activating circulating, cationic plasmid-bearing MBs with pulsed low-pressure (0.1 MPa) 1.1-MHz FUS facilitates sonoselective gene delivery to the endothelium without MRI-detectable disruption of the BBB. The degree of endothelial selectivity varied inversely with the FUS pressure, with higher pressures (i.e., 0.3-MPa and 0.4-MPa FUS) consistently inducing BBB opening and extravascular transfection. Bulk RNA sequencing analyses revealed that the sonoselective low-pressure regimen does not up-regulate inflammatory or immune responses. Single-cell RNA sequencing indicated that the transcriptome of sonoselectively transfected brain endothelium was unaffected by the treatment. The approach developed here permits targeted gene delivery to blood vessels and could be used to promote angiogenesis, release endothelial cellsecreted factors to stimulate nerve regrowth, or recruit neural stem cells.
Editor: United States: National Academy of Sciences
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Anterior Resultado 3 Avançar Ir para próxima página

Realização: Logos de Redes Sociais:

Sonoselective transfection of cerebral vasculature without blood–brain barrier disruption

Gorick, Catherine M. ; Mathew, Alexander S. ; Garrison, William J. ; Thim, E. Andrew ; Fisher, Delaney G. ; Copeland, Caitleen A. ; Song, Ji ; Klibanov, Alexander L. ; Miller, G. Wilson ; Price, Richard J.

United States: National Academy of Sciences

Buscando em bases de dados remotas. Favor aguardar.