Expression of Human Anti-Hemophilic Factor IX in the Milk of Transgenic Sheep

Clark, A. J.; Bessos, Hagop; Bishop, John O.; Brown, Pamela; Harris, Stephen; Lathe, Richard; McClenaghan, M; Prowse, Christopher V.; Simons, Paul; Whitelaw, Bruce; Wilmut, Ian

doi:10.1038/nbt0589-487

Cited by 134 publications

(44 citation statements)

References 24 publications

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“…The results of these analyses are summarized in Figure 5, which shows the extent of the 5' region included in each construct, the number of transgenic animals made with each construct, the number of integrated transgene copies, and the expression seen in these lines. Using constructs containing 5' flanking regions from the transcription start site up to positions -0.3 kb, -2.3 kb or -3.1 kb, we observed no expression in any of the transgenic lines (4)(5)(6) lines analyzed for each construct, see Fig. 5).…”

Section: Resultsmentioning

confidence: 86%

Tissue-specific expression in the salivary glands of transgenic mice

Mikkelsen

Brandt²,

Larsen³

et al. 1992

Nucl Acids Res

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Using a DNA construct, named Lama, derived from the murine parotid secretory protein (PSP) gene, we have obtained salivary gland specific gene expression in transgenic mice. Lama is a PSP minigene and allows analysis of the PSP gene 5' regulatory region by transgenesis. We show here that the regulatory region included in Lama with 4.6 kb of 5' flanking sequence is sufficient to direct expression specifically to the salivary glands. The expression level in the parotid gland is only about one percent of the PSP mRNA level, while that of the sublingual gland is near the PSP mRNA level. This suggests significant differences in the PSP gene regulation in the two glands. In addition, Lama is a secretory expression vector in which cDNAs or genomic fragments can be inserted. We demonstrate that the Lama construct can direct the expression of a heterologous cDNA encoding the C-terminal peptide of human factor Vil to salivary glands and that the corresponding peptide is secreted into saliva.

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Section: Resultsmentioning

confidence: 86%

Tissue-specific expression in the salivary glands of transgenic mice

Mikkelsen

Brandt²,

Larsen³

et al. 1992

Nucl Acids Res

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“…Bunun en kolay yolunun ise; hayvanların sütü, yumurtası, kanı, idrarı gibi vücut ürünlerinin veya sıvılarının olabileceği kanısına varılmış ve bazı canlıların tasarımı da bu amaca uygun şekilde planlanmıştır. Bu amaca uygun şekilde genetiği değiştirilen bir koyuna, eksikliğinde insanlarda hemofiliye neden olan Faktör IX geninin aktarılması ve hayvanın sütünde bu proteinin bol miktarda üretilmesi (19) ile kalıtsal anjiyoödem (20) veya yenidoğan Pompe hastalığının (21) tedavisinde kullanılan transgenik tavşan sütlerinin de yine insan sağlığı için kullanılması önerilmiştir. Bunlardan başka, diyabet tedavisi için kullanılan insülin, hemofili hastaları tarafından kullanılan pıhtılaşma faktörleri ile fibrinojen, antitrombin III, hemoglobin, serum albumini, doku plazminojen aktivatörü, alfa-1-antitripsin ile monoklonal antikorları içeren diğer terapötik proteinlerin de tasarımları ve sentezleri yine gen aktarımlı hayvanlar ile yapılmaktadır.…”

Section: Transgenik Canlıların Tıptaki Kullanımlarıunclassified

Biyoteknoloji, tıp ve etik

Üstün¹,

Demirci²

2016

Ege Tıp Dergisi

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ÖzGünümüzde öngörülenden çok daha hızlı gelişen biyoteknoloji uygulamaları, insan sağlığına yönelik olarak; yeni ilaçların üretilmesi, tedavi ya da deneysel amaçlı hormon, vitamin ve antibiyotikler gibi moleküllerin elde edilmesi, zarar görmüş dokuların işlevselliğini sağlayacak olan yapay dokuların yapılması ve hasarlı genlerin onarımlarını hedefleyen gen terapileri gibi uygulamaları içermektedir. Gen aktarımı yöntemleri sayesinde, kendi türü haricindeki bir türden bir gen parçası aktarılarak genomu değiştirilmiş olan ve bu özellikleri fenotipinde sergileyen "transgenik organizmalar/canlılar", günümüzde tıp, biyoloji, hayvancılık gibi yaşam bilimleri içinde geniş bir uygulama alanına sahip olsa da, dünya kamuoyundaki bilimsel ve siyasal platformlardaki gündemini korumaktadır. Bu derlemede, gen aktarım teknikleri ile elde edilen canlıların tıp alanındaki kullanımlarını ve bu kullanımın etik açıdan değerlendirilmesini amaçladık.Anahtar Sözcükler: Biyoteknoloji, transgenik organizmalar, gen aktarımı, etik. Abstract Today; biotechnology applications which developed much faster than expected covers; production and synthesis of molecules like of new drugs, hormones, vitamins and antibiotics, production of artificial tissues which will provide the functionality of damaged tissues and gene therapies to repair damaged genes. Even they have a wide range of applications in many different

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“…From a broad biochemical and physiological perspective, the pig is more closely related to humans than the ruminants, which include the cow, sheep, and goat. As an example of the differences between ruminant and pig biochemistry, recombinant FIX production in sheep was unsuccessful, with only low levels of biologically active FIX being produced: less than 0.5 ng of biologically active FIX could be recovered from each millilitre of milk [24]. The sheep was even less productive than donor plasma at 0.0001 U mL −1 of milk.…”

Section: Transgenic Animal Production Of Haemophilic Factorsmentioning

confidence: 99%

Haemophilic factors produced by transgenic livestock: abundance that can enable alternative therapies worldwide

et al. 2004

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SummaryHaemophilia replacement factors, both plasma-derived and recombinant, are in relatively short supply and are high-cost products. This has stymied the study and development of alternative methods of administration of haemophilia therapy even in the most economically advanced countries, owing to the large amounts of material needed because bioabsorption and bioavailability of haemophilic factors can be less than 10% when using non-intravenous routes of delivery. There is therefore a need to increase access to therapy worldwide by decreasing the cost and increasing the abundance so that therapy can be achieved through simplified, alternative delivery methods. Transgenic livestock have been used to produce haemophilic factors in milk. Only the pig mammary gland has been shown to carry out the post-translational processing necessary to enable both the biological activity and long circulation half-life needed for therapeutic glycoproteins. Furthermore, the large amounts of recombinant protein that can be produced from pig milk make feasible the use of alternative delivery methods such as oral, intratracheal, subcutaneous, and intramuscular administration.

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Expression of Human Anti-Hemophilic Factor IX in the Milk of Transgenic Sheep

Cited by 134 publications

References 24 publications

Tissue-specific expression in the salivary glands of transgenic mice

Tissue-specific expression in the salivary glands of transgenic mice

Biyoteknoloji, tıp ve etik

Haemophilic factors produced by transgenic livestock: abundance that can enable alternative therapies worldwide

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