Flotte Terence R
Powell Gene Therapy Center, Genetics Institute, Department of Pediatrics, University of Florida, 1600 SW Archer Rd., Box 100296, Gainesville, FL 32610-0296, USA.
Curr Gene Ther. 2005 Jun;5(3):361-6. doi: 10.2174/1566523054064986.
Recent studies have shed light on a number of important obstacles to safe and effective gene transfer to the respiratory tract with recombinant AAV vectors. Among these are blocks at the level of receptor binding and internalizations, evasion of proteasomal degradation, inefficiency of nuclear entry, and nuclear factors that inhibit the conversion of rAAV genomes into active double-stranded DNA form. Other important issues have been the size constraints of the vector, the lack of retention of episomal forms of the vector genome, and immune responses which may limit the efficiency of repeated doses of rAAV. Each of these potential obstacles has been addressed with new vector designs. In addition, the availability of an abundance of novel rAAV serotypes, each with its own receptor tropism, has expanded the range of possibilities for long-term success of gene therapy in the respiratory tract.
最近的研究揭示了使用重组腺相关病毒（AAV）载体向呼吸道进行安全有效基因转移的一些重要障碍。其中包括受体结合和内化水平的阻断、逃避蛋白酶体降解、核进入效率低下以及抑制rAAV基因组转化为活性双链DNA形式的核因子。其他重要问题包括载体的大小限制、载体基因组游离形式的保留不足以及可能限制rAAV重复给药效率的免疫反应。针对这些潜在障碍中的每一个，都采用了新的载体设计。此外，大量新型rAAV血清型的出现，每种血清型都有其自身的受体嗜性，扩大了呼吸道基因治疗长期成功的可能性范围。
