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【medical-news】肿瘤抑制性分子转运的改进
Print Submitted: 2009-8-27 17:16 Source: University of Iowa
A mouse tumor treated with an aptamer-siRNA combination (right) shows many dead areas (indicated by the asterisks), whereas an untreated tumor (left) is still largely intact. Delivering siRNA successfully to...
Small interfering RNA (siRNA), a type of genetic material, can block potentially harmful activity in cells, such as tumor cell growth. But delivering siRNA successfully to specific cells without adversely affecting other cells has been challenging.
University of Iowa researchers have modified siRNA so that it can be injected into the bloodstream and impact targeted cells while producing fewer side effects. The findings, which were based on animal models of prostate cancer, also could make it easier to create large amounts of targeted therapeutic siRNAs for treating cancer and other diseases. The study results appeared online Aug. 23 in the journal Nature Biotechnology.
"Our goal was to make siRNA deliverable through the bloodstream and make it more specific to the genes that are over expressed in cancer," said the study's senior author Paloma Giangrande, Ph.D., assistant professor of internal medicine and a member of Holden Comprehensive Cancer Center.
In previous research completed at Duke University, Giangrande's team showed that a compound called an aptamer can be combined with siRNA to target certain genes. When the combined molecule is directly injected into tumors in animal models, it triggers the processes that stop tumor growth. However, directly injecting the combination into tumors in humans is difficult.
In the new study, the researchers trimmed the size of a prostate cancer-specific aptamer and modified the siRNA to increase its activity. Upon injection into the bloodstream, the combination triggered tumor regression without affecting normal tissues.
Making the aptamer-siRNA combination smaller makes it easier to produce large amounts of it synthetically, Giangrande said.
The team also addressed the problem that large amounts of siRNA are needed since most of it gets excreted by the kidneys before having an effect. To keep siRNA in the body longer and thereby use less of it, the team modified it using a process called PEGlyation.
"If you want to use siRNA effectively for clinical use, especially for cancer treatment, you need to deliver it through an injection into the bloodstream, reduce the amount of side effects and be able to improve its cost-effectiveness. Our findings may help make these things possible," Giangrande said.
Although the current study focused on prostate cancer, the findings could apply to other cancers and diseases. Giangrande said the next step is to test the optimized aptamer-siRNA compound in a larger animal model 这篇也自己来翻译吧，48h U-Iowa improves delivery of cancer-fighting molecules
U-Iowa 改进抗肿瘤分子的转运
A mouse tumor treated with an aptamer-siRNA combination (right) shows many dead areas (indicated by the asterisks), whereas an untreated tumor (left) is still largely intact. Delivering siRNA successfully to...
小鼠肿瘤经过适体-siRNA结合治疗发现大量的死亡区域，而未接受治疗的肿瘤基本完整。
Small interfering RNA (siRNA), a type of genetic material, can block potentially harmful activity in cells, such as tumor cell growth. But delivering siRNA successfully to specific cells without adversely affecting other cells has been challenging.
小分子干扰RNA（siRNA）是一种遗传物质，潜在阻断细胞中的有害活动比如肿瘤细胞生长。但是很难做到成功转运siRNA到特定细胞中而没有损害其他细胞。
University of Iowa researchers have modified siRNA so that it can be injected into the bloodstream and impact targeted cells while producing fewer side effects. The findings, which were based on animal models of prostate cancer, also could make it easier to create large amounts of targeted therapeutic siRNAs for treating cancer and other diseases. The study results appeared online Aug. 23 in the journal Nature Biotechnology.
Iowa大学研究者修改了siRNA，将其注射入血液中，只影响靶定细胞并且产生少量副作用。这个发现是基于动物前列腺癌模型，更容易产生大量的靶向治疗的siRNAs，治疗肿瘤和其他疾病。研究结果发表在8月23日Nature Biotechnology杂志上。
"Our goal was to make siRNA deliverable through the bloodstream and make it more specific to the genes that are over expressed in cancer," said the study's senior author Paloma Giangrande, Ph.D., assistant professor of internal medicine and a member of Holden Comprehensive Cancer Center.
”我们的目标是使得siRNA转运进入血液，更加特异结合肿瘤中过表达的基因，”Holden Comprehensive肿瘤中心成员及内科医学助理教授Paloma Giangrande, Ph.D.,表示。
In previous research completed at Duke University, Giangrande's team showed that a compound called an aptamer can be combined with siRNA to target certain genes. When the combined molecule is directly injected into tumors in animal models, it triggers the processes that stop tumor growth. However, directly injecting the combination into tumors in humans is difficult.
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作者:admin@医学,生命科学 2010-10-04 17:11
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