ArticleMolecular biology reports2016
High-level expression of a novel recombinant human plasminogen activator (rhPA) in the milk of transgenic rabbits and its thrombolytic bioactivity in vitro.
Article in Molecular biology reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Characterization of Enlarged Tongues in Cloned Piglets.Current issues in molecular biology · 2023Article
- Evaluation of the α-casein (CSN1S1) locus as a potential target for a site-specific transgene integration.Scientific reports · 2022Article
- Identification, purification, and pharmacological activity analysis of Desmodus rotundus salivary plasminogen activator alpha1 (DSPAα1) expressed in transgenic rabbit mammary glands.Transgenic research · 2022Article
- Use of Genome Editing Techniques to Produce Transgenic Farm Animals.Advances in experimental medicine and biology · 2022Review
- Double-Gene Copromoting Expression Analysis in tPA/GH Transgenic Goat Mammary Epithelial Cells and Thrombolytic Activity of tPA In Vitro.BioMed research international · 2022Article
- [Preparation of GH/tPA double transgenic mice and gene expression analysis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- The goat β‑casein/CMV chimeric promoter drives the expression of hLF in transgenic goats produced by cell transgene microinjection.International journal of molecular medicine · 2019Article
- Accurately cleavable goat β-lactoglobulin signal peptide efficiently guided translation of a recombinant human plasminogen activator in transgenic rabbit mammary gland.Bioscience reports · 2019Article
- Structural Biology and Protein Engineering of Thrombolytics.Computational and structural biotechnology journal · 2019Review
- Spontaneous severe hypercholesterolemia and atherosclerosis lesions in rabbits with deficiency of low-density lipoprotein receptor (LDLR) on exon 7.EBioMedicine · 2018Article
- Production of functional human CuZn-SOD and EC-SOD in bitransgenic cloned goat milk.Transgenic research · 2018Article
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11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human tissue-type plasminogen activator (tPA) is a key kinase of fibrinolysis that plays an important role in dissolving fibrin clots to promote thrombolysis. The recombinant human plasminogen activator (rhPA) has more thrombolytic advantages than the wild type tPA. To increase the half-life and thrombolytic activity of tPA, a mutant containing only the essential K2 fibrin-binding and P activating plasminogen domains of the wild type tPA was cloned. This fragment was then inserted into goat β-casein regulatory sequences. Then, a mammary gland-specific expression vector, PCL25/rhPA, was constructed, and the transgenic rabbits were generated. In this study, 18 live transgenic founders (12♀, 6♂) were generated using pronuclear microinjection. Six transgenic rabbits were obtained, and the expression levels of rhPA in the milk had a range of 15.2-630 µg/ml. A fibrin agarose plate assay of rhPA showed that it had strong thrombolytic bioactivity in vitro, and the highest specific activity was >360 (360 times more than that of alteplase). The results indicated that the rhPA containing only the K2 and P domains is efficiently expressed with higher thrombolytic bioactivity in the milk of transgenic rabbits. Our study also demonstrated a new method for the large-scale production of clinically relevant recombinant pharmaceutical proteins in the mammary glands of transgenic rabbits.
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