上门推销产品的职员都知道成功的关键在于使顾客愿意打开产品来看看。现在，希望治愈肌肉营养不良症的基因治疗专家也发现了同样的事情：传递治疗性基因到肌肉组织中的秘诀在于血管。这一结果首次说明注射到血管中的基因能进入并整合到全身的特定的组织中。
肌肉营养不良的最常见形式——杜兴氏肌肉营养不良症（Duchenne）是由突变的dystrophin蛋白造成的。这种蛋白能重创身体中的所有肌肉，包括骨骼肌、心肌和膈肌（控制呼吸），并且这种疾病通常会导致患者在20岁左右时死亡。研究人员十多年来一直尝试替换dystophin基因。尽管他们曾经改造了一种携带正常dystrophin基因的感冒病毒，但研究人员却无法将正常dystrophin基因输送到全身每一块肌肉中。
人体血液循环
为了知道渗透全身的毛细血管是否有用，分子遗传学家Jeffrey Chamberlain及其华盛顿大学的同事首先将含有一种能使组织变蓝的蛋白的测试病毒注射到健康小鼠中，同时还注射了VEGF——一种使血管生长并使他们渗漏的化合物。实验发现，使用越多的VEGF，小鼠肌肉就会变的越蓝，这表明肌肉所含病毒的水平越高。非肌肉器官能吸收这种病毒，但不能产生颜色转化蛋白。研究组将VEGF和含有有用的dystrophin基因的病毒一起注射到缺失这个基因的小鼠中发现，得到补充的肌肉能更好地抵御损伤。只注射一次就能恢复dystrophin的正常水平并且阻止肌肉的降解。研究结果发布在7月25日的Nature Medicine的网络版上。
基因治疗专家Savio Woo说，这个结果简直是“异想天开”，并且是迈向基因治疗的重要一步。这项研究已经使Iowa大学的神经生物学家Beverly Davidson改变了她之前的看法。之前，她怀疑这种传递是否能完成。“他证明我错了，”她说。但她提醒说目前的大障碍将是如何将这种方法用在人类患者身上。
It's all in the delivery. Dystrophic mouse muscle treated with genes delivered via leaky blood vessels (bottom) looks more like healthy tissue (top) than untreated dystrophic muscle (middle).
ScienceNow-July 26,2004-More Muscle for Dystrophic Mice
Any door-to-door salesperson knows that the key to success is getting the customer to just open up. Now, gene therapists hoping to cure muscular dystrophy h
ave found the same thing: Getting blood vessels to open up is the secret to delivering a therapeutic gene to muscle tissue. The result shows for the first t
ime that genes injected into the bloodstream can be incorporated into a specific tissue type all over the body.
The most common form of muscular dystrophy, Duchenne muscular dystrophy, is caused by a mutant protein called dystrophin. The protein smites every muscle in
the body--including skeletal muscle, the heart, and the diaphragm, which controls breathing--and the disease usually kills its victims in their 20s. Researchers have been trying to replace the gene for dystrophin for more than a deca
de. Although they've engineered a common-cold virus to carry a corrected version of the dystrophin gene, researchers have had difficulty delivering the fix
to every muscle.
To see if leaky capillaries might help, molecular geneticist Jeffrey Chamberlain and colleagues at the University of Washington, Seattle, first injected hea
lthy mice with a test virus containing a protein that turns tissue blue, along with a compound called VEGF(vascular endothelium growth factor) that causes blood vessels to grow and makes them leaky in the process. The more VEGF they u
sed, the bluer the mice's muscles became, indicating higher levels of the virus. Nonmuscle organs took up the virus, but did not make the color-transforming protein. Encouraged, the team injected VEGF and the virus containing a functional copy of the dystrophin gene into mice lacking the gene. Eight weeks later, most of the muscles contained proper dystrophin, and the supplemented muscle
s resisted injury better. Just one injection could restore normal levels of dystrophin and prevent muscles from breaking down, the team reports online 25 Ju
ly in Nature Medicine.
The result is "fantastic" and a "major step forward" for gene therapy, says gene therapist Savio Woo of Mount Sinai School of Medicine in New York City. And
the research has made a convert of neurobiologist Beverly Davidson of the University of Iowa, Iowa City, who says she'd become skeptical that delivery to e
very muscle could be accomplished. "He proved me wrong," she says, but cautions that "the big hurdle will be how to translate that to a human patient."
original text:
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