Loading
Life sciences · Journal article
Drug Delivery · October 15, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
Efficient delivery of plasmid DNA (pDNA) into the nucleus remains a major bottleneck in nonviral gene therapy, particularly in post-mitotic and slowly dividing cells where the nuclear envelope constitutes a permanent barrier to passive entry. This review considers the two main strategies for active nuclear targeting: nuclear localisation signal (NLS) peptides, which recruit importin-α/β receptors directly to DNA cargo, and DNA nuclear targeting sequences (DTS), which exploit NLS-bearing transcription factors to mediate piggyback nuclear import. Rather than re-cataloguing nuclear import biology, we focus on the conditions under which each strategy succeeds or fails, incorporating advances in nuclear pore complex architecture and permeability, karyopherin-FG-nucleoporin electrostatics, and cytoplasmic constraints such as barrier-to-autointegration factor (BAF)-mediated clustering of exogenous DNA. NLS classes are compared with universal (SV40 enhancer), inducible (NF-κB) and tissue-specific (SMGA, SP-C, T1α) DTS elements, and four chemical coupling strategies are evaluated across peptide-, polymer- and lipid-based nanoassemblies. To address the near-absence of NLS/DTS mechanisms in current clinical pDNA programmes, we propose the Nuclear Accessibility Index (NAI): a three-axis framework integrating cell division status, carrier-DNA accessibility and intracellular signalling context. Treating the NAI as an axis vector rather than a summed score defines permissive, conditional and excluded regions of the design space. Two matter in practice: one in which highly proliferative cells render active targeting redundant, and one in which the rate-limiting problem is carrier engineering rather than the addition of a signal. The NAI offers design principles for nuclear-targeted nanocarriers and defines the preconditions for therapeutically relevant active import.