Williams Matthew L, Koch Walter J
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Annu Rev Physiol. 2004;66:49-75. doi: 10.1146/annurev.physiol.66.032102.141555.
In recent years there has been a rapid expansion in our understanding of the molecular biology that underpins human physiology. In the heart, elegant molecular pathways have been elucidated, and derangements in these pathways have been identified as factors in cardiac disease. However, as our understanding has grown, we have recognized that there exist only relatively crude tools to effect changes in molecular pathophysiology. The ultimate promise of gene therapy is to correct the molecular derangements that cause illness. To bring this promise to fruition in the clinical arena, many problems need to be solved, and chief among these remains reliable and robust delivery of genes to the target organ. To this end, viral vectors have been utilized with success more frequently than any other method of gene delivery. The use of these vectors in the heart has already offered promising novel benefit for human ischemic heart disease, and studies in animal models have given glimpses of hope that gene therapy may provide future therapeutic benefit in heart failure by improving cardiac function.
近年来，我们对作为人类生理学基础的分子生物学的理解有了迅速扩展。在心脏方面，精妙的分子途径已被阐明，并且这些途径的紊乱已被确定为心脏病的因素。然而，随着我们认识的加深，我们意识到在影响分子病理生理学变化方面，现有的工具相对粗糙。基因治疗的最终前景是纠正导致疾病的分子紊乱。为了在临床领域实现这一前景，需要解决许多问题，其中首要问题仍然是将基因可靠且有力地递送至靶器官。为此，病毒载体比任何其他基因递送方法更频繁地成功得到利用。这些载体在心脏中的应用已经为人类缺血性心脏病带来了有前景的新益处，并且在动物模型中的研究已经让人看到希望，即基因治疗可能通过改善心脏功能为心力衰竭提供未来的治疗益处。
