The use of the gastrointestinal tract as a site for the local delivery of DNA is an exciting prospect. In order to obtain an effective vector capable of delivering a gene of interest to target cells to achieve sufficient and sustained transgene expression, with minimal toxicity, we developed a new generation of filamentous bacteriophage. This particular bacteriophage was genetically engineered to display an arginine–glycine–aspartic acid (RGD) motif (an integrin-binding peptide) on the major coat protein pVIII and carry a mammalian DNA cassette. One unanticipated observation is the thermoresponsive behavior of engineered bacteriophage. This finding has led us to simplify the isolation method to purify bacteriophage particles from cell culture supernatant by low-temperature precipitation. Our results showed that in contrast to non-surface modified, the RGD-modified bacteriophage was successfully used to deliver a transgene to mammalian cells. Our in vitro model of the human intestinal follicle-associated epithelium also demonstrated that bacteriophage particles were stable in simulated gastrointestinal fluids and able to cross the human intestinal barrier. In addition, we confirmed an adjuvant property of the engineered bacteriophage to induce nitric oxide production by macrophages. In conclusion, our study demonstrated the possibility of using bacteriophage for gene transfer in the gastrointestinal tract.​

胃肠道作为局部递送DNA的场所的使用是令人兴奋的前景。为了获得能够将目的基因递送至靶细胞以实现充分且持续的转基因表达且毒性最小的有效载体，我们开发了新一代的丝状噬菌体。这种特殊的噬菌体经过基因工程改造，可显示出精氨酸主要外壳蛋白pVIII上的–甘氨酸-天冬氨酸（RGD）基序（一种整合素结合肽），带有哺乳动物DNA盒。一项意想不到的发现是工程噬菌体的热响应行为。这一发现使我们简化了通过低温沉淀从细胞培养上清液中纯化噬菌体颗粒的分离方法。我们的结果表明，与非表面修饰相比，RGD修饰的噬菌体已成功用于将转基因传递至哺乳动物细胞。我们的人肠滤泡相关上皮的体外模型还证明，噬菌体颗粒在模拟胃肠液中稳定，并且能够穿过人肠屏障。另外，我们证实了工程化噬菌体的佐剂性质可诱导巨噬细胞产生一氧化氮。总之，我们的研究证明了使用噬菌体在胃肠道进行基因转移的可能性。