Question

Part 1: Once ATryn has been produced in the goat's milk.

1. How is it harvested?

2. How is the drug manufactured?

3. How is the drug administered?

Part 2: How are iPSCs "genetically reprogrammed?" You must describe and discuss the genes for credit.

Answer 1

ATryn is the first medicine produced using genetically engineered animals. GTC states that one genetically modified goat can produce the same amount of antithrombin in a year as 90,000 blood donations.GTC chose goats for the process because they reproduce more rapidly than cattle and produce more protein than rabbits or mice.

ATryn is the brand name of the anticoagulant antithrombin manufactured by the Massachusetts-based U.S. company rEVO Biologics (formerly known as GTC Biotherapeutics).

Part 1:

1.) Atryn is made from the antithrombin harvested from the goat milk.

2.) It is made from the milk of goats that have been genetically modified to produce human antithrombin, a plasma protein with anticoagulant properties.

3.) Microinjection is used to insert human antithrombin genes into the cell nucleus of their embryos.

Part 2:

Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem cell (ESC)–like state by being forced to express genes such as Oct4, Sox2, c-Myc, and Klf4. iPSCs have been made from skin cells, immune cells, and other stem cells, such as mesenchymal stem cells and mobilized CD34+hematopoietic stem cells (HSCs). However, iPSCs have not been made from nonmobilized CD34+ HSCs in the peripheral blood until now.

Merling et al. derived iPSCs from a small volume of fresh or cryopreserved peripheral blood by reprogramming with an excisable loxP-flanked polycistronic lentiviral or nonintegrating Sendai viral vector. The loxP-flanked lentiviral vector resulted in 1 to 10 iPSC colonies from 20 mL of blood that were almost completely (>95%) reprogrammed. The Sendai viral vector gave variable colony yields (6 to >500) that were variably reprogrammed (10 to 80%). These iPSCs were capable of differentiating into all three germ layers in vitro and in vivo in teratoma assays. After excision of the loxP vectors by use of a transiently expressed Cre recombinase, the iPSCs retained the pluripotency markers, capacity for three germ layer formations, and their sample identity and origin. They also exhibited a normal karyotype and similar DNA methylation profiles to reference human ESC lines. Importantly, Merling and colleagues found that these iPSCs were not derived from lymphocytes or monocytes in the blood because they do not have the characteristic markers of these cells.