Dean D A
Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.
Adv Drug Deliv Rev. 2000 Nov 15;44(2-3):81-95. doi: 10.1016/s0169-409x(00)00087-9.
Peptide nucleic acids, or PNAs, are oligonucleotide analogs in which the phosphodiester backbone is replaced with a polyamide structure. First synthesized less than 10 years ago, they have received great attention due to their several favorable properties, including resistance to nuclease and protease digestion, stability in serum and cell extracts, and their high affinity for RNA and single and double-stranded DNA targets. Although initially designed and demonstrated to function as antisense and antigene reagents that inhibit both transcription and translation by steric hindrance, more recent applications have included gene activation by synthetic promoter formation and mutagenesis of chromosomal targets. Most notably for gene delivery, they have been used to specifically label plasmids and act as adapters to link synthetic peptides or ligands to the DNA. Thus, their great potential lies in the ability to attach specific targeting peptides to plasmids to circumvent such barriers to gene transfer as cell-targeting or nuclear localization, thereby increasing the efficacy of gene therapy.
肽核酸，即PNA，是一种寡核苷酸类似物，其磷酸二酯主链被聚酰胺结构所取代。它在不到10年前首次合成，因其具有多种优良特性而备受关注，这些特性包括抗核酸酶和蛋白酶消化、在血清和细胞提取物中的稳定性以及对RNA和单链及双链DNA靶标的高亲和力。尽管最初设计并证明其作为反义及反基因试剂，通过空间位阻抑制转录和翻译，但最近的应用还包括通过合成启动子形成进行基因激活以及对染色体靶标进行诱变。在基因递送方面最值得注意的是，它们已被用于特异性标记质粒，并作为衔接子将合成肽或配体与DNA连接。因此，它们的巨大潜力在于能够将特定的靶向肽连接到质粒上，以规避诸如细胞靶向或核定位等基因转移障碍，从而提高基因治疗的疗效。
