Glycoengineering of CHO cells to express recombinant alpha-1 antitrypsin

Ended Project Grant Awarded Last action

Award ID
R41HL164260
Recipient
Awarding agency
Obligated
$548,882

Award facts

Assistance listing
93.837 Cardiovascular Diseases Research
Completion date
Originally
Place of performance
Maryland, USA

Award details come from USAspending.gov.

Description

Abstract
Alpha-1 antitrypsin (A1AT) is well-established as a biotherapeutic used for the treatment of alpha-1 antitrypsin deficiency, and shows promise for treating a variety of other diseases. However, A1AT augmentation therapy carries unnecessary risk since IT relies upon the weekly transfusion of plasma-derived product, which presents supply chain and contaminant risks. This could be remedied with recombinant A1AT, if IT adequately matches or improves upon the plasma-derived product, including its post-translational modifications and functional attributes. However, major hurdles to the development of recombinant A1AT exist, since post- translational modifications, such as glycosylation, impact drug activities and half-life, and IT has remained challenging to match glycosylation of recombinant A1AT to the plasma derived isoforms. Here we developed a large panel of diverse GMP-ready glycoengineered CHO (gecho) cell lines that allowed US to discover a host cell line, gecho-l, that matches glycosylation of the plasma derived product. Here we will demonstrate our platform not only allows US to identify a CHO clone matches the glycosylation of the approved product, but that we can also match the function and half-life of the approved A1AT to enable the manufacturing of a recombinant A1AT to increase the safety and protect the supply of therapeutic A1AT. We further engineer the recombinant A1AT to obtain a product with improved activity and half-life as a candidate therapeutic for alpha-1 antitrypsin deficiency and other diseases.

Transactions

Action Obligated Date
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Amendment $274,441
Original award $274,441

Quick answers

Who received award R41HL164260?

R41HL164260 was awarded to Neuimmune, Inc. by National Heart Lung and Blood Institute (National Institutes of Health) on September 22, 2022.

How much is award R41HL164260 worth?

$548,882 has been obligated on R41HL164260.

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