ArticleScientific reports2015
Engineering protein processing of the mammary gland to produce abundant hemophilia B therapy in milk.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Evaluation of the α-casein (CSN1S1) locus as a potential target for a site-specific transgene integration.Scientific reports · 2022Article
- Use of Genome Editing Techniques to Produce Transgenic Farm Animals.Advances in experimental medicine and biology · 2022Review
- Review
- An exonic splicing enhancer mutation inDisease models & mechanisms · 2019Article
- Genome editing revolutionize the creation of genetically modified pigs for modeling human diseases.Human genetics · 2016Review
- A galactopoiesis accordant yield of functional recombinant human factor IX from homozygous transgenic pigs requires a large amount of vitamin K supplementation.Transgenic research · 2016Article
- One-step Multiplex Transgenesis via Sleeping Beauty Transposition in Cattle.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Both the low animal cell density of bioreactors and their ability to post-translationally process recombinant factor IX (rFIX) limit hemophilia B therapy to <20% of the world's population. We used transgenic pigs to make rFIX in milk at about 3,000-fold higher output than provided by industrial bioreactors. However, this resulted in incomplete γ-carboxylation and propeptide cleavage where both processes are transmembrane mediated. We then bioengineered the co-expression of truncated, soluble human furin (rFurin) with pro-rFIX at a favorable enzyme to substrate ratio. This resulted in the complete conversion of pro-rFIX to rFIX while yielding a normal lactation. Importantly, these high levels of propeptide processing by soluble rFurin did not preempt γ-carboxylation in the ER and therefore was compartmentalized to the Trans-Golgi Network (TGN) and also to milk. The Golgi specific engineering demonstrated here segues the ER targeted enhancement of γ-carboxylation needed to biomanufacture coagulation proteins like rFIX using transgenic livestock.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.