Glycoengineering of CHO cells to express recombinant alpha-1 antitrypsin
Glycoengineering of CHO cells to express recombinant alpha-1 antitrypsin
批准号:
10484110
负责人:
Nathan Enoch Lewis
金额:
$27.44万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-09-22 至 2024-09-21
关键词:
AnimalsBiological Response Modifier TherapyBlood CirculationBlood-Borne PathogensCell LineCellsChinese Hamster Ovary CellChronic Obstructive Pulmonary DiseaseClinicalClinical ResearchClinical TrialsComplexContractsDevelopmentDiseaseDrug KineticsEngineeringEnsureFrequenciesGenesGeneticGlycoengineeringGlycoproteinsHalf-LifeHumanINS geneIn VitroIncidenceKnock-outLeadLiver diseasesLung TransplantationModificationMutationPatient CarePerformancePharmaceutical PreparationsPlasmaPost-Translational Protein ProcessingPreparationPrionsProductionProtein EngineeringProtein IsoformsProteinsProteolysisPulmonary EmphysemaRattusRecombinant ProteinsRecombinantsReplacement TherapyRiskSafetySourceSystemTherapeuticTransfusionVariantalpha 1-Antitrypsinalpha 1-Antitrypsin Deficiencycostglycosylationimprovedin vitro activityin vivoliver transplantationoxidationpreclinical studystemtherapeutic candidate
中文摘要
摘要
英文摘要
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.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Glycoengineered recombinant alpha1-antitrypsin results in comparable in vitro and in vivo activities to human plasma-derived protein.
糖基工程重组 α1-抗胰蛋白酶的体外和体内活性与人血浆衍生蛋白相当。
DOI:
10.1101/2024.03.27.587088
发表时间:
2024
期刊:
bioRxiv : the preprint server for biology
影响因子:
--
作者:
[Rocamora,Frances, Schoffelen,Sanne, Arnsdorf,Johnny, Toth,EricA, Abdul,Yunus, Cleveland4th,ThomasE, Bjørn,SaraPetersen, Wu,MinaYingMin, McElvaney,NoelG, Voldborg,BjørnGunnarRude, Fuerst,ThomasR, Lewis,NathanE]
通讯作者:
Lewis,NathanE
ImmCellFIE: producing high-resolution snapshots of the functions of immune cells
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批准号:10199979
-
项目类别:
-
资助金额:$19.59万
-
财政年份:2020
-
负责人:Nathan Enoch Lewis
-
依托单位:
ImmCellFIE: producing high-resolution snapshots of the functions of immune cells
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批准号:10027185
-
项目类别:
-
资助金额:$24.94万
-
财政年份:2020
-
负责人:Nathan Enoch Lewis
-
依托单位:
Unraveling the mammalian secretory pathway through systems biology and algorithm development
-
批准号:10826657
-
项目类别:
-
资助金额:$7.58万
-
财政年份:2016
-
负责人:Nathan Enoch Lewis
-
依托单位:
Unraveling the mammalian secretory pathway through systems biology and algorithm development
-
批准号:10207258
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项目类别:
-
资助金额:$46.1万
-
财政年份:2016
-
负责人:Nathan Enoch Lewis
-
依托单位:
Unraveling the mammalian secretory pathway through systems biology and algorithm development
-
批准号:10413925
-
项目类别:
-
资助金额:$43.45万
-
财政年份:2016
-
负责人:Nathan Enoch Lewis
-
依托单位:
Unraveling the mammalian secretory pathway through systems biology and algorithm development
-
批准号:10654737
-
项目类别:
-
资助金额:$43.45万
-
财政年份:2016
-
负责人:Nathan Enoch Lewis
-
依托单位:
Unraveling the mammalian secretory pathway through systems biology and algorithm development
-
批准号:9142975
-
项目类别:
-
资助金额:$38.75万
-
财政年份:2016
-
负责人:Nathan Enoch Lewis
-
依托单位: