Application of Cloning to the Production of Biopharmaceuticals to Treat Human and Animal Disease
Eric Overström. Professor, Tufts University, School of Veterinary Medicine
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Health Care: Human & Animals
Nuclear Transfer – Cloning
Advantages
- Proven methodology in several species, recent reports of success in Sheep, cattle & pigs
- Good efficiency, < ~ 98% of offspring are transgenic, demonstrates stable transgene integration & expression
- Germline transgenesis
- Less costly due to transfection/selection in vitro
Disadvantages
- Methodology not optimized in domestic animals
- Strategies for “knockout” & “knockin” constructs
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Table 1. Development of caprine embryos reconstructed by
nuclear transfer using CFF6 transgenic fetal somatic cells
| Nuclear transfer protocols |
Metaphase
II |
Telophase
II-Ca |
Telophase
II- EtOH |
| Oocytes reconstructed |
138 |
92 |
55 |
| Oocyte lysis (%) |
67 (48.5) |
38 (41.3) |
23 (41.8) |
| Embryo cleavage (%) |
48 (34.8) |
41 (44.6) |
31 (58.4) |
| Embryos transferred (%) |
37 (34) |
38 (41.3) |
27 (49.1) |
| Recipients |
15 |
14 |
9 |
Ultrasound positive (%)
30 days |
9 (60) |
11 (78.6) |
5 (55.5) |
| 40 days |
1 (6.7) |
1 (7.1) |
0 |
| 60 days |
1 (6.7) |
1 (7.1) |
0 |
| Term pregnancy (%) |
1 (6.7) |
1 (7.1) |
0 |
| Offspring |
1 |
2 |
0 |
| % of embryos transferred |
2.1 |
5.2 |
0 |
| % of embryos reconstructed |
0.7 |
2.2 |
0 |
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Table 2. rhAT expression in CFF6-1 goat milk from an
induced lactation
CFF6-1 induced
Lactation day |
hAT concentration
(g/liter) |
hAT activity
(U/ml) |
| Day 3 |
4.7 |
N/D |
| Day 5 |
5.8 |
20.5 |
| Day 6 |
5.0 |
18.3 |
| Day 7 |
4.7 |
15.6 |
| Day 8 |
4.1 |
14.4 |
| Day 9 |
3.7 |
14.6 |
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N/D: not determined |
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Summary
- Rational application of animal cloning to the production of
biopharmaceuticals
- Benefit to human and animal health
- Animal welfare is not compromised
- Advance fundamental understanding of mechanism that regulate normal and
abnormal cell growth
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Email
link | Feedback | Contributed by: Boston University. Video adapted from the
Issues for the Millennium Workshop
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