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Abstract：
Gene therapy is extensively studied as a realistic and promising therapeutic approach for treating inherited and acquired diseases by repairing defective genes through introducing (transfection) the \"healthy\" genetic material in the diseased cells. To succeed, the proper DNA or RNA fragments need efficient vectors, and viruses are endowed with excellent transfection efficiency and have been extensively exploited. Due to several drawbacks related to their use, nonviral cationic materials, including lipidic, polymeric, and dendrimer vectors capable of electrostatically interacting with anionic phosphate groups of genetic material, represent appealing alternative options to viral carriers. Particularly, dendrimers are highly branched, nanosized synthetic polymers characterized by a globular structure, low polydispersity index, presence of internal cavities, and a large number of peripheral functional groups exploitable to bind cationic moieties. Dendrimers are successful in several biomedical applications and are currently extensively studied for nonviral gene delivery. Among dendrimers, those derived by 2,2-bis(hydroxymethyl)propanoic acid (b-HMPA), having, unlike PAMAMs, a neutral polyester-based scaffold, could be particularly good-looking due to their degradability in vivo. Here, an overview of gene therapy, its objectives and challenges, and the main cationic materials studied for transporting and delivering genetic materials have been reported. Subsequently, due to their high potential for application in vivo, we have focused on the biodegradable dendrimer scaffolds, telling the history of the birth and development of b-HMPA-derived dendrimers. Finally, thanks to a personal experience in the synthesis of b-HMPA-based dendrimers, our contribution to this field has been described. In particular, we have enriched this work by reporting about the b-HMPA-based derivatives peripherally functionalized with amino acids prepared by us in recent years, thus rendering this paper original and different from the existing reviews.
摘要：
基因治疗被广泛研究为通过在患病细胞中引入（转染）“健康”遗传物质修复缺陷基因来治疗遗传和获得性疾病的现实和有希望的治疗方法。为了成功,正确的DNA或RNA片段需要有效的载体，和病毒具有优异的转染效率，并已被广泛利用。由于与它们的使用有关的几个缺点，非病毒阳离子材料，包括脂质,聚合物,和能够与遗传物质的阴离子磷酸盐基团静电相互作用的树枝状聚合物载体，代表病毒携带者有吸引力的替代选择。特别是,树枝状聚合物是高度分支的，以球状结构为特征的纳米级合成聚合物，低的多分散指数，内部空腔的存在，和大量可用于结合阳离子部分的外周官能团。树枝状聚合物在几种生物医学应用中是成功的,并且目前被广泛研究用于非病毒基因递送。在树枝状聚合物中，由2,2-双（羟甲基）丙酸（b-HMPA）衍生的那些，having,与PAMAM不同，中性聚酯基支架，由于它们在体内的降解性，可能特别好看。这里,基因治疗的概述，其目标和挑战，并且已经报道了用于运输和递送遗传物质的主要阳离子材料。随后，由于它们在体内的高应用潜力，我们专注于可生物降解的树枝状支架，讲述了b-HMPA衍生的树枝状聚合物的诞生和发展历史。最后,由于在合成基于b-HMPA的树枝状聚合物方面的个人经验，我们对这一领域的贡献已经描述过了。特别是,我们通过报道近年来我们制备的基于b-HMPA的氨基酸外周官能化衍生物丰富了这项工作，从而使本文具有原创性，不同于现有的评论。
