Spinal subpial delivery of AAV9 enables widespread gene silencing and blocks motoneuron degeneration in ALS

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F20%3A00523984" target="_blank" >RIV/61389013:_____/20:00523984 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985904:_____/20:00523984

Výsledek na webu

<a href="https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=45859139767" target="_blank" >https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=45859139767</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41591-019-0674-1" target="_blank" >10.1038/s41591-019-0674-1</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Spinal subpial delivery of AAV9 enables widespread gene silencing and blocks motoneuron degeneration in ALS

Popis výsledku v původním jazyce

Gene silencing with virally delivered shRNA represents a promising approach for treatment of inherited neurodegenerative disorders. In the present study we develop a subpial technique, which we show in adult animals successfully delivers adeno-associated virus (AAV) throughout the cervical, thoracic and lumbar spinal cord, as well as brain motor centers. One-time injection at cervical and lumbar levels just before disease onset in mice expressing a familial amyotrophic lateral sclerosis (ALS)-causing mutant SOD1 produces long-term suppression of motoneuron disease, including near-complete preservation of spinal alpha-motoneurons and muscle innervation. Treatment after disease onset potently blocks progression of disease and further alpha-motoneuron degeneration. A single subpial AAV9 injection in adult pigs or non-human primates using a newly designed device produces homogeneous delivery throughout the cervical spinal cord white and gray matter and brain motor centers. Thus, spinal subpial delivery in adult animals is highly effective for AAV-mediated gene delivery throughout the spinal cord and supraspinal motor centers.

Název v anglickém jazyce

Spinal subpial delivery of AAV9 enables widespread gene silencing and blocks motoneuron degeneration in ALS

Popis výsledku anglicky

Gene silencing with virally delivered shRNA represents a promising approach for treatment of inherited neurodegenerative disorders. In the present study we develop a subpial technique, which we show in adult animals successfully delivers adeno-associated virus (AAV) throughout the cervical, thoracic and lumbar spinal cord, as well as brain motor centers. One-time injection at cervical and lumbar levels just before disease onset in mice expressing a familial amyotrophic lateral sclerosis (ALS)-causing mutant SOD1 produces long-term suppression of motoneuron disease, including near-complete preservation of spinal alpha-motoneurons and muscle innervation. Treatment after disease onset potently blocks progression of disease and further alpha-motoneuron degeneration. A single subpial AAV9 injection in adult pigs or non-human primates using a newly designed device produces homogeneous delivery throughout the cervical spinal cord white and gray matter and brain motor centers. Thus, spinal subpial delivery in adult animals is highly effective for AAV-mediated gene delivery throughout the spinal cord and supraspinal motor centers.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Medicine

ISSN

1078-8956

e-ISSN

—

Svazek periodika

26

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

118-130

Kód UT WoS článku

000509831900035

EID výsledku v databázi Scopus

2-s2.0-85076913952