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为宠物“节育”无需手术——免疫疗法
(用于人类,指日可待)

每日科学(2011.3.31)-Weill Cornell Medical College的研究者证实可通过免疫哺乳动物的方法节育(孕)。他们谈到,该技术也可以用于其它哺乳动物-包括人类-因为生育激素及其受体为非种属特异性且男性和女性之间具有相似性。对于宠物,该技术可作为节育和激素注射副作用的替代疗法。

在2月24日在线版的Genetic Engineering and Biotechnology Journal中,研究者称他们新合成一种嵌合基因,该基因可产生具有抗原性的双功能重组蛋白。这种抗体可以降低女性孕酮及男性睾丸激素的产生。

本研究主要项目负责人Weill Cornell Medical College的Brij B. Saxena博士谈到,该技术近期可用于控制狗、猫或其他需要控制数量的哺乳动物。在进行大规模动物前临床有效性、安全性和可逆性试验后,研究者认为,这种免疫疗法也可能用于人类治疗雄激素过多综合征以及采用免疫学手段进行节育(孕)。

这一新型嵌合基因是由Saxena博士与其同事Meirong Hao 和Premila Rathnam共同制备的。他们将其插入昆虫细胞表达重组双功能蛋白。通过利用重组蛋白主动免疫或被动免疫产生双功能抗体以拮抗受孕。

新基因含有来自两个天然基因的DNA序列,这两个基因编码哺乳动物受孕相关的蛋白。一部分是结合于人类促黄体素/人类促绒毛膜性腺激素受体(存在于卵巢和睾丸表面)的配体胞外区,另一部分是人类促绒毛性腺激素β-亚单位C末端的共有序列。

建立新嵌合基因和重组蛋白的关键是研究者发现hLH-R与hCG-β-CTP重组蛋白具有抗原性,这意味着其可诱导机体发生免疫应答,产生具有两种功能的双功能抗体。这一抗体可以阻断激素与其受体结合,继而抑制卵巢产生分泌激素的信号,尤其是孕酮。抗体的第二个成分与hCG-β-CTP相结合,可以中和受精卵或在着床时出现的hCG样功能。这将导致缺乏刺激黄体产生孕酮的信号,从而导致内皮细胞无法增殖,而这是受精卵着床的关键,因此终止妊娠。

科学家现在正致力于制备用于狗和猫实验的重组嵌合蛋白质抗原。

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翻译

Immune Therapy Can Control Fertility in Mammals: Technique Could Prevent Pregnancy in Pets, Human Use Is Also Envisioned
为宠物“节育”无需手术——免疫疗法
不久将来也许亦会应用于人类

ScienceDaily (Mar. 31, 2011) — Researchers at Weill Cornell Medical College have shown that it is possible to immunize mammals to control fertility. They say their technique could possibly be used on other mammals -- including humans -- because fertility hormones and their receptors are species-non-specific and are similar in both females and males. For pets, the technique could be an alternative to castration and adverse effects of hormone administration.
每日科学(2011.3.31)-Weill Cornell Medical College的研究者证实可通过免疫哺乳动物的方法节育(孕)。他们谈到,他们的技术也可以用于其它扑入动物-包括人类-因此生育激素及其受体为非种属特异性且在男女间相似的物质。对于宠物,该技术可作为节育和激素注射副作用的替代疗法。

In the Feb. 24 online issue of Genetic Engineering and Biotechnology Journal, the researchers say their newly synthesized novel chimeric genes produce bi-functional recombinant proteins that are antigenic. The antibodies can tamp down production of progesterone in females and testosterone in males. The most immediate use of this technique might be to control fertility in dogs and cats or other mammals in need of population control, says the study's lead investigator, Dr. Brij B. Saxena, the Harold and Percy Uris Professor of Reproductive Biology at Weill Cornell Medical College.
在2月24日在线版的Genetic Engineering and Biotechnology Journal中,研究者称他们新合成一种嵌合基因产物,具有抗原性的双功能重组蛋白。该抗体可以降低女性孕酮及男性睾丸激素的产生。本研究主要项目负责人Weill Cornell Medical College的Brij B. Saxena博士谈到,该技术可用于控制狗、猫或其他需要控制数量的哺乳动物。

After extensive preclinical testing for the efficacy, safety and reversibility in animals, the immune therapy might be possible in humans as a treatment for androgen excess syndromes as well as an immunological method to control fertility, adds Dr. Saxena.
Saxena博士说,在对动物进行了大规模的前临床有效性、安全性和可逆性试验后,这种免疫疗法也可能用于人类治疗雄激素过多综合征以及采用免疫学手段进行节育(孕)。

The new chimeric gene was engineered by Dr. Saxena and his Weill Cornell colleagues, Dr. Meirong Hao and Dr. Premila Rathnam, and then inserted into insect cells to produce recombinant bi-functional protein. Immunity against fertility can be provided by the production of a bi-functional antibody by active or passive immunization using the recombinant protein.
这一新型嵌合基因是有Saxena博士与其同事Meirong Hao 和Premila Rathnam共同制备的,随后他们将其插入昆虫细胞表达重组双功能蛋白。通过利用重组蛋白主动免疫或被动免疫产生双功能抗体以拮抗受孕。

This new gene contains DNA sequences from two natural genes that are integral to fertility in mammals. One portion is the extracellular domain (ECD) of the ligand (hormone) binding region of the human lutropin/human chorionic gonadotropin receptor (ECD-hLH-R), which is present in the ovaries and testes. The other component is the unique C-terminal peptide of the human chorionic gonadotropin β-subunit (hCG β-CTP).
新基因含有来自两个天然基因的DNA序列,这两个基因编码哺乳动物受孕相关。一部分是结合于人类促黄体素/人类促绒毛膜性腺激素受体(存在于卵巢和睾丸表面)的配体胞外区,另一部分是人类促绒毛性腺激素β-亚单位C末端的共有序列。

Key to development of this new chimeric gene and recombinant protein is the researchers' finding that the hLH-R and hCG-β-CTP recombinant proteins are antigenic -- meaning that they can produce an immune response in the body, and produce bifunctional antibodies with dual effect. The antibodies are able to block the hormone binding to the receptor and thus suppress the signal to produce ovarian hormones, specifically progesterone. The second component of the antibody specific to hCG β-CTP would neutralize the hCG-like material produced by the fertilized egg prior to or at the time of implantation. This would lead to lack of stimulation to promote progesterone production by the corpus luteum, resulting in the lack of proliferation of endometrial growth that is vital for the implantation of the fertilized egg -- thus preventing pregnancy.
建立新嵌合基因和重组蛋白的关键是研究者发现Hlh-R与hCG-β-CTP重组蛋白具有抗原性,这意味着他们可以诱导机体发生免疫应答,产生具有两种功能的双功能抗体。这一抗体可以阻断激素与其受体结合,继而一直卵巢产生分泌激素的信号,尤其是孕酮。抗体的第二个成分与hCG-β-CTP相结合,可以中和受精卵或在着床时出现的hcG样功能。这将导致缺乏刺激黄体产生孕酮的信号,从而导致内皮细胞无法增殖,而这是受精卵着床的关键,因此终止妊娠。

The scientists are now working on methods to upscale the production of recombinant chimeric protein to be tested as antigens in dogs and cats.
科学家现在正致力于制备用于狗和猫实验的重组嵌合蛋白质抗原。

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