The local production of therapeutic proteins has generated considerable interest in the research community as a strategy to overcome the challenges associated with conventional protein-based therapies, such as high costs, the inconvenience of repeated administrations, and unwanted side effects. This review explores the potential of targeted polymeric nanoparticles that carry nucleic acids to induce controlled, localized production of therapeutic antibodies. Polymeric nanoparticles are analyzed on the basis of four key components: (1) the polymer matrix, including cationic, non-cationic, lipid-polymer hybrid, and cyclodextrin-based systems; (2) the genetic payload designed for antibody production; (3) linker chemistry, ranging from standard covalent bonds to stimuli-responsive or non-covalent bonds; and (4) potential targeting tools such as antibodies/fragments, peptides, or aptamers, for identifying target cells. By combining gene therapy with nanomedicine, these particles reduce immune responses and show great promise for treating cancer, infections, and autoimmune diseases. To this end, their structure is discussed in relation to the therapeutic antibody’s mechanism of action and to their in vivo validation as a next-generation platform for antibody-based immunotherapies.
Antisense oligonucleotide gapmers degrade target RNA in a sequence-specific and RNase H-dependent manner and are emerging as a promising antiviral strategy. Locked nucleic acid-modified gapmers have shown activity against several pathogenic viruses. Tick-borne encephalitis virus is widely distributed across Eurasia, with approximately 10,000 cases reported annually, and the absence of approved therapies represents a significant public health concern. In this study, we designed 71 locked nucleic acid-modified gapmers targeting structural elements within the untranslated regions of the single-stranded positive-sense RNA genome of tick-borne encephalitis virus. The antiviral efficacy of gapmers selected via in silico analysis was evaluated using a replicon system and infectious virus assays. Gapmers targeting stem-loop structures in the 3′ untranslated region effectively inhibited viral replication. Optimizing the length and composition of the lead gapmers further enhanced antiviral potency. Sequence alignment analysis revealed that the target regions of the optimized gapmers were highly conserved among the three major subtypes of tick-borne encephalitis virus. Accordingly, the optimized gapmers markedly inhibited replication of a highly pathogenic strain, suggesting broad-spectrum activity. Collectively, our findings support the development of locked nucleic acid-modified gapmers as therapeutics against tick-borne encephalitis virus and other tick-borne flaviviruses.
