Asset Details
Do you wish to reserve the book?
Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency
Do you wish to request the book?
Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency
2020
Overview
Alpha 1-antitrypsin (AAT) deficiency arises from an inherited mutation in the SERPINA1 gene. The disease causes damage in the liver where the majority of the AAT protein is produced. Lack of functioning circulating AAT protein also causes uninhibited elastolytic activity in the lungs leading to AAT deficiency-related emphysema. The only therapy apart from liver transplantation is augmentation with human AAT protein pooled from sera, which is only reserved for patients with advanced lung disease caused by severe AAT deficiency. We tested modified mRNA encoding human AAT in primary human hepatocytes in culture, including hepatocytes from AAT deficient patients. Both expression and functional activity were investigated. Secreted AAT protein increased from 1,14 to 3,43 µg/ml in media from primary human hepatocytes following mRNA treatment as investigated by ELISA and western blot. The translated protein showed activity and protease inhibitory function as measured by elastase activity assay. Also, mRNA formulation in lipid nanoparticles was assessed for systemic delivery in both wild type mice and the NSG-PiZ transgenic mouse model of AAT deficiency. Systemic intravenous delivery of modified mRNA led to hepatic uptake and translation into a functioning protein in mice. These data support the use of systemic mRNA therapy as a potential treatment for AAT deficiency.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/109
/ 13/51
/ 14/35
/ 38/77
/ 42/109
/ 42/35
/ 692/4017
/ 82/80
/ A1 gene
/ alpha 1-Antitrypsin - genetics
/ alpha 1-Antitrypsin - physiology
/ alpha 1-Antitrypsin Deficiency - genetics
/ alpha 1-Antitrypsin Deficiency - therapy
/ Animals
/ Elastase
/ Enzyme-Linked Immunosorbent Assay
/ Humanities and Social Sciences
/ Humans
/ mRNA
/ Proteins
/ Science
