DNA is indisputably another archetypal charge-dense polyanion that dominates biology. Being the guardian of the genetic information in humans and almost all other organisms, it is likely the most studied biological macromolecule. And, since upon unlocking the secrets of the human genome it was discovered that nearly all diseases have a genetic component, the biomedical interest in DNA for gene therapy has dramatically increased in recent years [4]. The Food and Drug Administration (FDA) defines gene-based therapeutics as “products that mediate their effects by transcription and/or translation of transferred genetic material and/or by integrating into the host genome and that are administered as nucleic acids, viruses, or genetically engineered micro-organisms. The products may be used to modify cells in vivo or transferred to cells ex vivo prior to administration to the recipient [5]”. Thus, the opportunity to treat such disorders by replacing the defective gene(s) with normal (healthy) one(s) offers a novel therapeutic approach for patients who suffer from such diseases. However, to be successful in the clinics gene, therapy largely relies on the adoption of safe, effective, and efficient viral/non-viral nanovectors to transfer DNA to mammalian cells both ex vivo and in vivo [6]. In the plethora of currently available nanocarriers for gene delivery dendrimers, i.e., nanosized, hyperbranched, and self-similar molecules represent prototypical vectors with fine-tunable properties for optimal DNA delivery [7]. Their peculiar structure is constituted by three distinct domains (Figure 1c): (1) A fundamental atom, or most frequently, a group of atoms defined as the core; (2) the branching units, which, emanating from the core through diverse chemical reactions, allow the dendrimeric molecule to grow in geometrically organized radial layers known as generations (G); and (3) an exponentially increasing number peripheral surface groups, which constitute a multivalent nanoscale array, and can therefore form high-affinity interactions with a variety of biological targets, including nucleic acids [8,9,10]. However, high generation dendrimer synthesis is extremely laborious and time-consuming, since the final product purification is difficult and hampered by the presence of highly similar side products. Thus, notwithstanding the highly promising results achieved with these molecules, the difficulties inherent in large-scale good manufacturing practice (GMP) production of high generation dendrimers are hampering their way to the clinics [11]. One way to circumvent these obstacles and to make multivalent systems which are synthetically simpler and more responsive is to design low molecular weight amphiphilic dendrons which, upon spontaneous self-assembly into dendrimer-like nanovectors, can mimic (and eventually outperform) their covalent counterparts in size, shape, and functions [12,13,14,15,16,17,18,19,20].