Efficient Nucleic Acid Delivery Research Articles

Integrating Porous Silicon Nanoneedles within Medical Devices for Nucleic Acid Nanoinjection.

Porous silicon nanoneedles can interface with cells and tissues with minimal perturbation for high-throughput intracellular delivery and biosensing. Typically, nanoneedle devices are rigid, flat, and opaque, which limits their use for topical applications in the clinic. We have developed a robust, rapid, and precise substrate transfer approach to incorporate nanoneedles within diverse substrates of arbitrary composition, flexibility, curvature, transparency, and biodegradability. With this approach, we integrated nanoneedles on medically relevant elastomers, hydrogels, plastics, medical bandages, catheter tubes, and contact lenses. The integration retains the mechanical properties and transfection efficiency of the nanoneedles. Transparent devices enable the live monitoring of cell-nanoneedle interactions. Flexible devices interface with tissues for efficient, uniform, and sustained topical delivery of nucleic acids ex vivo and in vivo. The versatility of this approach highlights the opportunity to integrate nanoneedles within existing medical devices to develop advanced platforms for topical delivery and biosensing.

Synthesis of Amino Acid-Based Cationic Lipids and Study of the Role of the Cationic Head Group for Enhanced Drug and Nucleic Acid Delivery.

Leveraging liposomes for drug and nucleic acid delivery, though promising due to reduced toxicity and ease of preparation, faces challenges in stability and efficiency. To address this, we synthesized cationic amphiphiles from amino acids (arginine, lysine, and histidine). Histidine emerged as the superior candidate, leading to the development of three histidine-rich cationic amphiphiles for liposomes. Using the hydration method, we have prepared the liposomes and determined the optimal N/P ratios for lipoplex formation via gel electrophoresis. In vitro transfection assays compared the efficacy of our lipids to Fugene, while MTT assays gauged biocompatibility across cancer cell lines (MDA-MB 231 and MCF-7). The histidine-based lipid demonstrated marked potential in enhancing drug and nucleic acid delivery. This improvement stemmed from increased zeta potential, enhancing electrostatic interactions with nucleic acids and cellular uptake. Our findings underscore histidine's crucial role over lysine and arginine for effective delivery, revealing a significant correlation between histidine abundance and optimal performance. This study paves the way for histidine-enriched lipids as promising candidates for efficient drug and nucleic acid delivery, addressing key challenges in the field.

Recent Progress in the Endosomal Escape Mechanism and Chemical Structures of Polycations for Nucleic Acid Delivery.

Nucleic acid-based therapies are seeing a spiralling surge. Stimuli-responsive polymers, especially pH-responsive ones, are gaining widespread attention because of their ability to efficiently deliver nucleic acids. These polymers can be synthesized and modified according to target requirements, such as delivery sites and the nature of nucleic acids. In this regard, the endosomal escape mechanism of polymer-nucleic acid complexes (polyplexes) remains a topic of considerable interest owing to various plausible escape mechanisms. This review describes current progress in the endosomal escape mechanism of polyplexes and state-of-the-art chemical designs for pH-responsive polymers. The importance is also discussed of the acid dissociation constant (i.e., pKa) in designing the new generation of pH-responsive polymers, along with assays to monitor and quantify the endosomal escape behavior. Further, the use of machine learning is addressed in pKa prediction and polymer design to find novel chemical structures for pH responsiveness. This review will facilitate the design of new pH-responsive polymers for advanced and efficient nucleic acid delivery.

Conjugated Polyelectrolyte/Single Strand DNA Hybrid Polyplexes for Efficient Nucleic Acid Delivery and Targeted Protein Degradation

Conjugated Polyelectrolyte/Single Strand DNA Hybrid Polyplexes for Efficient Nucleic Acid Delivery and Targeted Protein Degradation

Theranostic siRNA loaded mesoporous silica nanoplatforms: A game changer in gene therapy for cancer treatment

Growing interest has been seen in non-pathogenic, safe, and effective gene therapy delivery systems. There are many nucleic acid therapies that have been studied to alter the expression of DNA or RNA, such as mRNA, siRNA, antisense DNA, and microRNA (miRNA), of which siRNA has been shown to be useful in blocking specific genes. The development of an efficient nucleic acid delivery method is crucial for molecular diagnostic and therapeutic systems. Mesoporous silica nanoparticles (MSNs) with high porosity, good textural qualities, and biocompatibility have been studied for use in drug delivery systems. They are being utilized more and more in combination therapy, gene silencing, and other biological applications, especially in cancer nanomedicine. MSNs offer efficient drug loading and controlled release, and additions can change their characteristics. They are widely employed in target medication delivery, biosensing, cellular uptake, and diagnostics in the biomedical field. Additionally, they have been connected to theranostic drugs for cancer treatment. This review highlights the current state of knowledge of MSNs and their specialized applications as theranostic agents for cancer management.

Constructing Nucleic Acid Delivering Lipoproteoplexes from Coiled-Coil Supercharged Protein and Cationic Liposomes.

The safe and efficient delivery of nucleic acids is crucial for both clinical applications of gene therapy and pre-clinical laboratory research. Such delivery strategies rely on vectors to condense nucleic acid payloads and escort them into the cell without being degraded in the extracellular environment; however, the construction and utilization of these vectors can be difficult and time-consuming. Here, we detail the steps involved in the rapid, laboratory-scale production and assessment of a versatile, nucleic acid delivery vehicle, known as the lipoproteoplex. In this chapter, we outline: (1) the recombinant synthesis and subsequent purification of the supercharged coiled-coil protein component known as N8; (2) the synthesis of cationic liposomes from dioleoyl-3-trimethylammonium propane (DOTAP) and sodium cholate; (3) and finally a protocol for the delivery of a model siRNA cargo into a cultured cell line.

PH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Fluorinated amphiphilic Poly(β-Amino ester) nanoparticle for highly efficient and specific delivery of nucleic acids to the Lung capillary endothelium

Endothelial cell dysfunction occurs in a variety of acute and chronic pulmonary diseases including pulmonary hypertension, viral and bacterial pneumonia, bronchopulmonary dysplasia, and congenital lung diseases such as alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). To correct endothelial dysfunction, there is a critical need for the development of nanoparticle systems that can deliver drugs and nucleic acids to endothelial cells with high efficiency and precision. While several nanoparticle delivery systems targeting endothelial cells have been recently developed, none of them are specific to lung endothelial cells without targeting other organs in the body. In the present study, we successfully solved this problem by developing non-toxic poly(β-amino) ester (PBAE) nanoparticles with specific structure design and fluorinated modification for high efficiency and specific delivery of nucleic acids to the pulmonary endothelial cells. After intravenous administration, the PBAE nanoparticles were capable of delivering non-integrating DNA plasmids to lung microvascular endothelial cells but not to other lung cell types. IVIS whole body imaging and flow cytometry demonstrated that DNA plasmid were functional in the lung endothelial cells but not in endothelial cells of other organs. Fluorination of PBAE was required for lung endothelial cell-specific targeting. Hematologic analysis and liver and kidney metabolic panels demonstrated the lack of toxicity in experimental mice. Thus, fluorinated PBAE nanoparticles can be an ideal vehicle for gene therapy targeting lung microvascular endothelium in pulmonary vascular disorders.

PH-responsive polyzwitterion covered nanocarriers for DNA delivery

The success of gene therapy relies on gene nanocarriers to achieve therapeutic effects in vivo. Surface shielding of poly(ethylene glycol) (PEG), known as PEGylation, onto gene delivery carriers is a predominant strategy for extending blood circulation and improving therapeutic outcomes in vivo. Nevertheless, PEGylation frequently compromises the transfection efficiency by decreasing the interactions with the cellular membrane of the targeted cells, thereby preventing the cellular uptake and the subsequent endosomal escape. Herein, we developed a stepwise pH-responsive polyplex micelle for the plasmid DNA delivery with the surface covered by ethylenediamine-based polycarboxybetaines. This polyplex micelle switched its surface charge from neutral at pH 7.4 to positive at tumorous and endo−/lysosomal pH (i.e., pH 6.5 and 5.5, respectively), thus enhancing the cellular uptake and facilitating the endosomal escape toward efficient gene transfection. Additionally, the polyplex micelle demonstrated prolonged blood circulation as well as enhanced tumor accumulation, leading to highly effective tumor growth suppression by delivering an antiangiogenic gene. These results suggest the usefulness of a pH-responsive charge-switchable shell polymer on the surface of the polyplex micelle for the efficient nucleic acid delivery.

Smart Nanocarriers for the Targeted Delivery of Therapeutic Nucleic Acid for Cancer Immunotherapy.

A wide variety of therapeutic approaches and technologies for delivering therapeutic agents have been investigated for treating cancer. Recently, immunotherapy has achieved success in cancer treatment. Successful clinical results of immunotherapeutic approaches for cancer treatment were led by antibodies targeting immune checkpoints, and many have advanced through clinical trials and obtained FDA approval. A major opportunity remains for the development of nucleic acid technology for cancer immunotherapy in the form of cancer vaccines, adoptive T-cell therapies, and gene regulation. However, these therapeutic approaches face many challenges related to their delivery to target cells, including their in vivo decay, the limited uptake by target cells, the requirements for nuclear penetration (in some cases), and the damage caused to healthy cells. These barriers can be avoided and resolved by utilizing advanced smart nanocarriers (e.g., lipids, polymers, spherical nucleic acids, metallic nanoparticles) that enable the efficient and selective delivery of nucleic acids to the target cells and/or tissues. Here, we review studies that have developed nanoparticle-mediated cancer immunotherapy as a technology for cancer patients. Moreover, we also investigate the crosstalk between the function of nucleic acid therapeutics in cancer immunotherapy, and we discuss how nanoparticles can be functionalized and designed to target the delivery and thus improve the efficacy, toxicity, and stability of these therapeutics.

Self-Assembly of Peptide-Lipid Nanoparticles for the Efficient Delivery of Nucleic Acids.

A transfection formulation is successfully developed to deliver nucleic acids by adding an auxiliary lipid (DOTAP) to the peptide, and the transfection efficiency of pDNA reaches 72.6%, which is close to Lipofectamine 2000. In addition, the designed KHL peptide-DOTAP complex exhibits good biocompatibility by cytotoxicity and hemolysis analysis. The mRNA delivery experiment indicates that the complex had a 9- or 10-fold increase compared with KHL or DOTAP alone. Intracellular localization shows that KHL/DOTAP can achieve good endolysosomal escape. Our design provides a new platform for improving the transfection efficiency of peptide vectors.

Advances and Challenges of Stimuli-Responsive Nucleic Acids Delivery System in Gene Therapy.

Gene therapy has emerged as a powerful tool to treat various diseases, such as cardiovascular diseases, neurological diseases, ocular diseases and cancer diseases. In 2018, the FDA approved Patisiran (the siRNA therapeutic) for treating amyloidosis. Compared with traditional drugs, gene therapy can directly correct the disease-related genes at the genetic level, which guarantees a sustained effect. However, nucleic acids are unstable in circulation and have short half-lives. They cannot pass through biological membranes due to their high molecular weight and massive negative charges. To facilitate the delivery of nucleic acids, it is crucial to develop a suitable delivery strategy. The rapid development of delivery systems has brought light to the gene delivery field, which can overcome multiple extracellular and intracellular barriers that prevent the efficient delivery of nucleic acids. Moreover, the emergence of stimuli-responsive delivery systems has made it possible to control the release of nucleic acids in an intelligent manner and to precisely guide the therapeutic nucleic acids to the target site. Considering the unique properties of stimuli-responsive delivery systems, various stimuli-responsive nanocarriers have been developed. For example, taking advantage of the physiological variations of a tumor (pH, redox and enzymes), various biostimuli- or endogenous stimuli-responsive delivery systems have been fabricated to control the gene delivery processes in an intelligent manner. In addition, other external stimuli, such as light, magnetic fields and ultrasound, have also been employed to construct stimuli-responsive nanocarriers. Nevertheless, most stimuli-responsive delivery systems are in the preclinical stage, and some critical issues remain to be solved for advancing the clinical translation of these nanocarriers, such as the unsatisfactory transfection efficiency, safety issues, complexity of manufacturing and off-target effects. The purpose of this review is to elaborate the principles of stimuli-responsive nanocarriers and to emphasize the most influential advances of stimuli-responsive gene delivery systems. Current challenges of their clinical translation and corresponding solutions will also be highlighted, which will accelerate the translation of stimuli-responsive nanocarriers and advance the development of gene therapy.

Lipoic Acid-Based Poly(disulfide)s as Versatile Biomolecule Delivery Vectors and the Application in Tumor Immunotherapy.

Intracellular delivery of therapeutic biomacromolecules, including nucleic acids and proteins, attracts extensive attention in biotherapeutics for various diseases. Herein, a strategy is proposed for the construction of poly(disulfide)s for the efficient delivery of both nucleic acids and proteins into cells. A convenient photo-cross-linking polymerization was adopted between disulfide bonds in two modified lipoic acid monomers (Zn coordinated with dipicolylamine analogue (ZnDPA) and guanidine (GUA)). The disulfide-containing main chain of the resulting poly(disulfide)s was responsive to reducing circumstance, facilitating the release of cargos. By screening the feeding ratio of ZnDPA and GUA, the resulting poly(disulfide)s exhibited better performance in the delivery of nucleic acids including plasmid DNA and siRNA than commercially available transfection reagents. Cellular uptake results revealed that the polymer/cargo complexes entered the cells mainly following a thiol-mediated uptake pathway. Meanwhile, the polymer could also efficiently deliver proteins into cells without an obvious loss of protein activity, showing the versatility of the poly(disulfide)s for the delivery of various biomacromolecules. Moreover, the in vivo therapeutic effect of the materials was verified in the E.G7-OVA tumor-bearing mice. Ovalbumin-based nanovaccine induced a strong cellular immune response, especially cytotoxic T lymphocyte cellular immune response, and inhibited tumor growth. These results revealed the promise of the poly(disulfide)s in the application of both gene therapy and immunotherapy.

704/DNA vaccines leverage cytoplasmic DNA stimulation to promote anti-HIV neutralizing antibody production in mice and strong immune response against alpha-fetoprotein in non-human primates

Genetic immunization is an attractive approach for prophylactic and therapeutic vaccination using synthetic vectors to deliver antigen-encoding nucleic acids. Recently, DNA delivered by a physical means or RNA by liposomes consisting of four different lipids demonstrated good protection in human phase III clinical trials and received Drugs Controller General of India and US FDA approval to protect against COVID-19, respectively. However, the development of a system allowing for efficient and simple delivery of nucleic acids while improving immune response priming has the potential to unleash the full therapeutic potential of genetic immunization. DNA-based gene therapies and vaccines have the potential for rapid development, as exemplified by the recent approval of Collategene, a gene therapy to treat human critical limb ischemia, and ZyCoV, a DNA vaccine delivered by spring-powered jet injector to protect against SARS-CoV2 infection. Recently, we reported amphiphilic block copolymer 704 as a promising synthetic vector for DNA vaccination in various models of human diseases. This vector allows dose sparing of antigen-encoding plasmid DNA. Here, we report the capacity of 704-mediated HIV and anti-hepatocellular carcinoma DNA vaccines to induce the production of specific antibodies against gp120 HIV envelope proteins in mice and against alpha-fetoprotein antigen in non-human primates, respectively. An investigation of the underlying mechanisms showed that 704-mediated vaccination did trigger a strong immune response by (1) allowing a direct DNA delivery into the cytosol, (2) promoting an intracytoplasmic DNA sensing leading to both interferon and NF-κB cascade stimulation, and (3) inducing antigen expression by muscle cells and presentation by antigen-presenting cells, leading to the induction of a robust adaptive response. Overall, our findings suggest that the 704-mediated DNA vaccination platform is an attractive method to develop both prophylactic and therapeutic vaccines.

Silencing of heat shock protein 90 (hsp90): Effect on development and infectivity of Ichthyophthirius multifiliis

BackgroundRecently, an increasing number of ichthyophthiriasis outbreaks has been reported, leading to high economic losses in fisheries and aquaculture. Although several strategies, including chemotherapeutics and immunoprophylaxis, have been implemented to control the parasite, no effective method is available. Hence, it is crucial to discover novel drug targets and vaccine candidates against Ichthyophthirius multifiliis. For this reason, understanding the parasite stage biology, host–pathogen interactions, molecular factors, regulation of major aspects during the invasion, and signaling pathways of the parasite can promote further prospects for disease management. Unfortunately, functional studies have been hampered in this ciliate due to the lack of robust methods for efficient nucleic acid delivery and genetic manipulation. In the current study, we used antisense technology to investigate the effects of targeted gene knockdown on the development and infectivity of I. multifiliis. Antisense oligonucleotides (ASOs) and their gold nanoconjugates were used to silence the heat shock protein 90 (hsp90) of I. multifiliis. Parasite stages were monitored for motility and development. In addition, the ability of the treated parasites to infect fish and cause disease was evaluated.ResultsWe demonstrated that ASOs were rapidly internalized by I. multifiliis and distributed diffusely throughout the cytosol. Knocking down of I. multifiliis hsp90 dramatically limited the growth and development of the parasite. In vivo exposure of common carp (Cyprinus carpio) showed reduced infectivity of ASO-treated theronts compared with the control group. No mortalities were recorded in the fish groups exposed to theronts pre-treated with ASOs compared with the 100% mortality observed in the non-treated control fish.ConclusionThis study presents a gene regulation approach for investigating gene function in I. multifiliis in vitro. In addition, we provide genetic evidence for the crucial role of hsp90 in the growth and development of the parasite, suggesting hsp90 as a novel therapeutic target for successful disease management. Further, this study introduces a useful tool and provides a significant contribution to the assessing and understanding of gene function in I. multifiliis.

Recent progress and applications of poly(beta amino esters)-based biomaterials.

Poly(beta-amino esters, PBAEs) are a promising class of cationic polymers synthesized from diacrylates and amines via Michael addition. Recently, PBAEs have been widely developed for drug delivery, immunotherapy, gene therapy, antibacterial, tissue engineering and other applications due to their convenient synthesis, good bio-compatibility and degradation properties. Herein, we mainly summarize the recent progress in the PBAEs synthesis and their applications. The amine groups of PBAEs could be protonated in low pH environment, exhibiting proton sponge and pH-sensitive abilities. Furthermore, the positive PBAEs can interact with negative genes via electrostatic interactions for efficient delivery of nucleic acids. Moreover, positive PBAEs could also directly kill bacteria by disrupting their membranes at high doses. Finally, PBAEs can augment the immune responses, and improve the bioactivity of hydrogels in tissue engineering.

DNA Nanoribbon for Efficient Anti-miRNA Peptide Nucleic Acid Delivery and Synergistic Enhancement of Cancer Cell Apoptosis.

Antisense peptide nucleic acid (asPNA), an effective antisense drug, has been employed as a gene therapy agent and a useful tool in molecular biology. Gaining control over the delivery of asPNA to target tissues has been a major hindrance to its wide application in clinical practice. A simple and efficient DNA nanoribbon (DNR)-based drug delivery process has been designed in this study that releases the asPNA agent to inhibit oncogenic microRNAs (miRNAs). Furthermore, we demonstrated how the AS1411 aptamer that binds nucleolin on the cell membranes works as a control mechanism capable of identifying target cancer cells and enhancing the enrichment capacity of DNR. With the biodegradability of DNR, we can efficiently initiate the release of asPNA into the cytoplasm, particularly targeting the intended miR-21 and synergistically increasing programmed cell death 4 (PDCD4) expression to enhance cell apoptosis. We assume that this well-defined delivery mechanism will aid in designing antisense site-specific treatments for various diseases, including cancer.

Lipofectamine 2000™ at transfection dose promotes EphA2 transcription in an HDAC4-dependent manner to reduce its cytotoxicity

The cationic liposome is well-known as an efficient nucleic acid delivery tool; however, the stress responses induced by liposome per se have been rarely revealed. In this study, we found that Lipofectamine™ 2000 (lipo2000), a commonly used commercial cationic liposome transfection, could upregulate EphA2 mRNA expression in multiple cells at transfection dose. Furthermore, lipo2000 treatment could increase the level of EphA2 hnRNA (heterogeneous nuclear RNA). Lipo2000-induced EphA2 upregulation could be depleted upon global transcription inhibition, proving that lipo2000 upregulates EphA2 expression via activating its transcription. Moreover, HDAC4 depletion, a known EphA2 trans-acting regulatory factor, could eliminate the lipo2000-induced EphA2 upregulation, demonstrating that lipo2000 promotes EphA2 transcription in an HDAC4 dependent manner. Functionally, EphA2 knockdown did not affect GFP expression level and the interfering efficacy of siGAPDH, suggesting that EphA2 is unrelated to the nucleic acid delivery capacity of lipo2000. Nevertheless, EphA2 depletion significantly activated autophagy and apoptosis, increasing the cytotoxic effects of lipo2000, which could be rescued by EphA2 restoration, indicating that EphA2 is essential to overcome liposome-related cytotoxicity. Finally, we found that lipo2000 could activate EphA2 transcription in an HDAC4-dependent manner. EphA2 is not associated with the transfection efficiency of lipo2000, but it is vital to reduce lipo2000 cytotoxicity, suggesting that when conducting liposome-mediated gene function studies, especially for EphA2, the stress response of liposomes should be considered to obtain objective results.

Designed Peptide Assemblies for Efficient Gene Delivery.

The safe and efficient delivery of nucleic acids including DNA, mRNA, siRNA, and miRNA into targeted cells is critical for gene therapy. Currently, viral gene vectors are very popular, but they have potential toxicity and insecurity. Therefore, the development of nonviral vectors has attracted considerable research attention. Peptide assemblies are superior candidates for being used as gene vectors by having good biocompatibility, versatile molecular design, excellent assembly capacity, ease of modification, and stimuli responsivity. The de novo designed peptides not only can induce efficient condensation of nucleic acids into compacted nanoparticles and protect them from enzymatic digestion but also can effectively overcome biological barriers and improve gene delivery efficiency through targeted delivery, enhanced cellular uptake, improved endolysosomal escape, and nuclear importation. By having these merits, peptidic gene vectors are developing fast, showing outstanding advantages compared to liposome and polymer vectors. This Perspective focuses on peptidic gene delivery systems by emphasizing the molecular design strategies for meeting the criteria of gene condensation, protection from nuclease degradation, cellular uptake, endolysosomal escape, and so on. The new arising research area of peptide-based artificial viruses for gene and ribonucleoprotein delivery has also been reviewed. The challenges and future perspectives are put forward, aiming to provide a conclusive guide for the development of peptidic delivery systems to achieve efficient gene therapy.

Nanoparticles for vaccine and gene therapy: Overcoming the barriers to nucleic acid delivery.

Nucleic acid therapeutics can be used to control virtually every aspect of cell behavior and therefore have significant potential to treat genetic disorders, infectious diseases, and cancer. However, while clinically approved to treat a small number of diseases, the full potential of nucleic acid therapeutics is hampered by inefficient delivery. Nucleic acids are large, highly charged biomolecules that are sensitive to degradation and so the approaches to deliver these molecules differ significantly from traditional small molecule drugs. Current studies suggest less than 1% of the injected nucleic acid dose is delivered to the target cell in an active form. This inefficient delivery increases costs and limits their use to applications where a small amount of nucleic acid is sufficient. In this review, we focus on two of the major barriers to efficient nucleic acid delivery: (1) delivery to the target cell and (2) transport to the subcellular compartment where the nucleic acids are therapeutically active. We explore how nanoparticles can be modified with targeting ligands to increase accumulation in specific cells, and how the composition of the nanoparticle can be engineered to manipulate or disrupt cellular membranes and facilitate delivery to the optimal subcellular compartments. Finally, we highlight how with intelligent material design, nanoparticle delivery systems have been developed to deliver nucleic acids that silence aberrant genes, correct genetic mutations, and act as both therapeutic and prophylactic vaccines. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.