Long-term erythropoietin expression in rodents and non-human primates following intramuscular injection of a replication-defective adenoviral vector.
Long-term erythropoietin expression in rodents and non-human primates following intramuscular injection of a replication-defective adenoviral vector.
复制标题
肌内注射复制缺陷型腺病毒载体后，啮齿动物和非人灵长类动物中促红细胞生成素的长期表达。
DOI：
10.1089/hum.1997.8.15-1797
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Leiden,JM
中科院分区：
文献类型：
--
作者：
Svensson,EC;Black,HB;Dugger,DL;Tripathy,SK;Goldwasser,E;Hao,Z;Chu,L;Leiden,JM
促红细胞生成素（Epo）反应性贫血是慢性肾衰竭和人类免疫缺陷病毒（HIV）感染的一种使人衰弱的并发症，影响超过15万美国人。Epo反应性贫血患者目前接受重组人Epo重复注射治疗。在本报告所述的研究中，我们检查了使用单次肌内（i.m.）注射编码Epo的复制缺陷型腺病毒载体（RDAd）用于治疗小鼠和非人灵长类动物中的Epo应答性贫血。我们的研究结果表明，有一个阈值剂量的病毒（2.5-8 × 107 pfu/克体重），这是需要获得长期的Epo表达和红细胞增多症在这两个物种。单一肌内给小鼠注射109 pfu的编码鼠Epo的RDAd（AdmEpo）导致血细胞比容从对照值49 ± 0.9%升高到治疗值81 ± 3%，其稳定超过1年。同样，一个单一的i.m.向猴注射4 × 1011 pfu的RDAd编码猿Epo（AdsEpo），导致血细胞比容从对照水平40%升高至给药水平≥ 70%，并稳定84天。用AdsEpo肌肉注射猴子似乎是安全的，因为在84天的实验时间过程中，我们没有检测到胸部X射线、血清化学、血液学或凝血特征（除了血细胞比容升高）或器官组织学的异常。总之，这些结果表明使用i.m.注射RDAd用于治疗人的Epo-应答性贫血。
Erythropoietin (Epo)-responsive anemia is a debilitating complication of chronic renal failure and human immunodeficiency virus (HIV) infection that effects more than 150,000 Americans. Patients with Epo-responsive anemias are currently treated with repeated injections of recombinant human Epo. In the studies described in this report, we have examined the safety and efficacy of using a single intramuscular (i.m.) injection of replication-defective adenoviral vectors (RDAd) encoding Epo for the treatment of Epo-responsive anemias in both mice and non-human primates. Our results demonstrate that there is a threshold dose of virus (2.5–8 × 107pfu/gram of body weight) which is required to obtain long-term Epo expression and polycythemia in both species. A single i.m. injection of mice with 109pfu of an RDAd encoding murine Epo (AdmEpo) resulted in elevations in hematocrits from control values of 49 ± 0.9% to treated values of 81 ± 3%, which were stable for more than 1 year. Similarly, a single i.m. injection of a monkey with 4 × 1011pfu of an RDAd-encoding simian Epo (AdsEpo) resulted in elevations of hematocrits from control levels of 40% to treated levels of ≥70%, which were stable for 84 days. Intramuscular injection of monkeys with AdsEpo appeared to be safe in that we did not detect abnormalities in chest X-rays, serum chemistries, hematologic, or clotting profiles (apart from elevated hematocrits) or organ histologies during the 84-day time course of the experiment. Taken together, these results suggest the feasibility of using i.m. injection of RDAd for the treatment of Epo-responsive anemias in humans.
登录
查看更多内容
DOI：
10.1073/pnas.93.24.14082
发表时间：
1996-11-26
影响因子：
11.1
作者：
Kessler, PD;Podsakoff, GM;Byrne, BJ
通讯作者：
Byrne, BJ
发育阶段、给药途径和免疫系统对腺病毒介导的基因转移的影响。
影响因子：
5.1
作者：
Kass-Eisler,A;Falck-Pedersen,E;Elfenbein,DH;Alvira,M;Buttrick,PM;Leinwand,LA
通讯作者：
Leinwand,LA
影响因子：
56.9
作者：
BARR, E;LEIDEN, JM
通讯作者：
LEIDEN, JM
非人灵长类动物对含有人囊性纤维化跨膜电导调节剂 cDNA 的腺病毒载体气道递送的急性反应。
影响因子：
4.2
作者：
Steven L. Brody;Mark Metzger;Claire Danel;M. Rosenfeld;Ronald G. Crystal
通讯作者：
Ronald G. Crystal
直接基因转移至小鼠骨骼肌后四环素调节的基因表达
DOI：
10.1007/bf02255778
发表时间：
1995
期刊：
Somatic Cell and Molecular Genetics
影响因子：
--
作者：
J. Dhawan;T. Rando;S. Elson;H. Bujard;H. Blau
通讯作者：
H. Blau