Design And Optimization Of Nucleic Acid Delivery Systems For Clinical Applications: A Review

Precision chemical engineering of dendrimers for nucleic acid delivery

Polymeric Delivery Vehicles for Nucleic Acid Vaccines: Design Strategies and Biological Barriers.

This review systematically dissects how functional polymer engineering-including interfacial shielding, targeted ligand modification, membrane perturbation, and stimuli-responsive disassembly-facilitates systemic circulation, antigen-presenting cell uptake, endosomal escape, and intracellular cargo release.

Mechanistic advances in nanomedicine, nucleic acid therapies, and AI-driven research on cervical cancer.

A translational framework for overcoming key barriers in pharmaceutical intervention design for oncology applications is outlined, integrating drug delivery engineering, molecular biopharmaceutics, and computational optimization.

Optimizing nucleic acid delivery using PF14 peptide and lipid nanoparticle systems

Nucleic acid–based therapeutics are a rapidly expanding class of precision medicines capable of directly modulating gene expression. However, their clinical application is limited by challenges in cellular delivery, including large molecular size, hydrophilicity, and susceptibility to enzymatic degradation. To address these barriers, advanced delivery platforms such as cell-penetrating peptides and lipid nanoparticles (LNPs) have been developed. This study evaluates two delivery systems: the cell-penetrating peptide PepFect-14 (PF14) and LNP formulations, for enhancing nucleic acid delivery and cellular uptake. PF14 facilitates intracellular transport through peptide–nucleic acid complex formation, while LNPs protect cargo from degradation and can promote endosomal escape. Their performance was assessed under different conditions using luciferase-based reporter systems in HeLa cells. PF14-mediated delivery of the splice-switching oligonucleotide ON-705 in HeLa 705 cells showed efficient splice correction, with activity increasing in a dose- and molar ratio- dependent manner, reaching a plateau at a 1:10 ratio. Delivery efficiency was significantly influenced by formulation conditions, with Opti-MEM outperforming standard media and sugar-based buffers. Polymer excipients also affected activity as PVA18, PVA40, and PVP40 enhanced performance, while low molecular weight PVP reduced efficacy. In parallel, LNP-mediated delivery of luciferase mRNA in wild-type HeLa cells demonstrated robust, dose-dependent protein expression. Both systems maintained high cell viability (80–100%). Overall, these findings highlight the importance of formulation optimization in improving nucleic acid delivery and provide practical insights for enhancing peptide- and lipid-based therapeutic platforms.

Lipid-Based Delivery Systems for Therapeutic Glycoproteins: Current Advances, Challenges, and Future Perspectives

Therapeutic glycoproteins, a pivotal class of biopharmaceuticals, have transformed modern medicine through their broad applications in oncology, immunotherapy, and infectious disease management. Their structural complexity and biological specificity make them highly effective in targeting disease pathways; however, challenges related to stability, bioavailability, and delivery efficacy limit their full potential. Recent advancements in delivery technologies have sought to address these challenges through innovative approaches such as nanotechnology-based carriers, controlled-release systems, and molecular engineering. These strategies have demonstrated the ability to enhance glycoprotein stability, optimize pharmacokinetics, and achieve targeted delivery with minimal off-target effects. This review provides a comprehensive overview of state-of-the-art lipid-based delivery systems specifically designed to overcome the unique pharmaceutical challenges associated with therapeutic glycoproteins, highlighting their design principles, formulation strategies, mechanisms of encapsulation and release, and therapeutic advantages in improving glycoprotein stability, bioavailability, targeted delivery, and treatment efficacy. In addition to surveying the current landscape, this review delves into the key challenges impeding the widespread adoption of advanced delivery systems, including immunogenicity, manufacturing scalability, and clinical translation. The review concludes with insights into emerging trends in the development of lipid-based delivery systems, positioning glycoprotein therapeutics at the forefront of innovation in biopharmaceuticals. This overview of advancements and challenges aims to provide a roadmap for future progress in the field of glycoprotein delivery and therapeutic applications.

Advances in the development and delivery of nucleic acid-based therapeutics.

Recent advancements in experimental and computational methods along with growing gene sequencing libraries have enabled rapid development of nucleic acid-based therapeutic design for a wide variety of diseases. New drugs, delivery tools and methods have enabled precise and efficient therapy at a molecular scale. This review covers the current landscape and future directions of methods for gene and cell therapies, as well as their applications, advantages, and limitations. We present self-amplifying RNA, circular RNA, CRISPR systems, antisense oligonucleotides, and antibody-oligonucleotide conjugates, as well as CAR modification of T-cells, natural killer cells, and macrophages, with a brief discussion of modified stem cells. We also discuss developments in viral and non-viral delivery systems for their applications in cell and gene therapies.