In vivo analysis of intramuscular gene transfer in human subjects studied by on-line ultrasound imaging.
In vivo analysis of intramuscular gene transfer in human subjects studied by on-line ultrasound imaging.
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通过在线超声成像研究人体肌肉内基因转移的体内分析。
DOI：
10.1089/10430340152480267
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发表时间：
2001
影响因子：
4.2
通讯作者：
Isner,JM
中科院分区：
文献类型：
--
作者：
Rauh,G;Pieczek,A;Irwin,W;Schainfeld,R;Isner,JM
目前的研究旨在验证一种假设，即肌肉内注射裸DNA会导致注射剂分布在远离针头放置位置的地方，这一发现可能会促进注射基因转移。采用经皮超声成像技术在线监测连续18例患者288例静脉注射期间，phvegf165溶液在骨骼肌组织中的分布程度。288个肌肉部位中有237个（82.3%）注射到小腿远端肌肉。在288个肌肉部位中的51个（17.7%），在足背的第一和/或第二骨间肌进行了注射。未受干扰的肌肉是由一个特征性的回声，点状纹理，边界是更强烈的回声筋膜。将i.m.基因转染到小腿肌肉时，注射物沿纵向尺寸分布为3.59±0.79 cm (1.39 ~ 5.87 cm)；在线平面测量对应的注射面积为1.83±0.51 cm2（0.62-3.41 cm2）。在足部骨间肌进行i.m.基因转移时，注射分布的纵向范围为2.49±0.66 cm (1.61 ~ 3.91 cm)，相应的注射面积为1.71±0.54 cm2（0.51 ~ 2.86 cm2）。这些发现证实，通过直接注射到肢体骨骼肌的质粒DNA溶液分布在针头进入的位置之外。因此，在不同部位进行多次注射可能会导致注射的DNA广泛分布，这是一个可能促进裸DNA和/或其他基因转移策略的物理因素。
The current study was designed to test the hypothesis that intramuscular (i.m.) injection of naked DNA leads to distribution of the injectate remote from the site of needle placement, a finding that might be expected to facilitate i.m. gene transfer. Transcutaneous ultrasound imaging was employed to monitor online the extent to which a solution of phVEGF165was distributed among the skeletal musculature during 288 i.m. injections in 18 consecutive patients. In 237 (82.3%) of 288 muscle sites, the injection was performed into the distal calf muscle. In 51 (17.7%) of 288 muscle sites, injection was performed into the first and/or second interosseous muscles of the dorsal foot. Unperturbed muscle was recognized by a characteristic echogenic, stippled texture that was bounded by more intensely echogenic fascia. When i.m. gene transfer was performed into the calf muscles, the injectate was distributed along a longitudinal dimension of 3.59 ± 0.79 cm (1.39-5.87 cm); the corresponding area of injectate measured by on-line planimetry was 1.83 ± 0.51 cm2(0.62-3.41 cm2). When i.m. gene transfer was performed into the interosseous muscles of the foot, the longitudinal extent of injectate distribution was 2.49 ± 0.66 cm (1.61-3.91 cm), with a corresponding injectate area of 1.71 ± 0.54 cm2(0.51-2.86 cm2). These findings establish that a solution of plasmid DNA administered by direct i.m. injection into the skeletal muscles of the limb is distributed well beyond the site of needle entry. Thus, the use of multiple injections performed at different sites is likely to result in broad distribution of DNA injectate, a physical factor that may act to facilitate naked DNA and/or other gene transfer strategies.