Delivery Platform Research Articles

Consumers’ usage of errand delivery services: The effects of service quality and consumer perception

Errand delivery services refer to a novel delivery form where individuals assist in receiving or distributing items for a certain fee. It has emerged due to consumption upgrading, the rise of the lazy economy, and especially the impact of epidemics such as the recent COVID-19 pandemic. This study aims to fill research gaps, a new second-order Q-ETAM structural equation model based on service quality and technology acceptance models constructed to investigate consumers' motivation to use errand delivery services and how service quality affects their perceptions, which in turn impacts their usage of these services. The results show that service quality and consumer perception significantly positively affect consumers' use of errand delivery services. Tangibles have the greatest effect among the second-order variables of errand delivery quality. Furthermore, consumers' perceived usefulness and ease of use significantly and positively mediate their intention to continue to use these services. In addition, consumers' perceived usefulness and intention to continue using errand delivery services play a significant chain mediating role. This study explores the external and internal factors affecting the usage of errand delivery services from the consumer's perspective and comprehensively explains these motivating factors. The research findings provide insights into errand delivery platforms' design, management strategies, and potential service expansion. These findings can enable enterprises to attract consumers, enhance satisfaction, and better compete in the last-mile delivery landscape, ultimately benefiting both the consumers and businesses participating in the courier delivery ecosystem.

Towards the preparation of smart drug delivery platforms for colorectal cancer therapy: Biocompatible and targeted mesoporous silica nanoparticles with the deferiprone-copper complex gatekeeper

BackgroundAchieving smart drug release and preventing premature leakage throughout the delivery journey are two crucial factors that are essential to take into account in the design of nanocarriers. Mesoporous silica nanoparticles (MSNs) can be modified with gatekeeper molecules to achieve controlled release behavior, making them highly promising nanocarriers for smart drug delivery purposes. MethodsHerein, we introduced a novel gatekeeper in the form of an inverted umbrella, consisting of a deferiprone (DFP)-copper complex, which was strategically immobilized on the surface of MSNs to facilitate smart and controlled release of doxorubicin (DOX) within tumor cells. Polyethylene glycol (PEG) polymer and aptamer were further added onto the surface of the nanocarrier to enhance its biocompatibility, and targeting capabilities. The physicochemical characteristics of the targeted nanoplatform, Apt-PEG-DOX@GNP, were investigated, and its anti-cancer effect was evaluated against C26 cells and CHO cells to assess its specificity. In order to evaluate the anti-tumor efficacy, possible side effects, and biodistribution of the prepared nanocarriers, the in vivo experiment was carried out on BALB/c mice bearing colorectal tumors. ResultsThe substantial surface area of MSNs, measuring 339 m2/g, facilitated effective encapsulation of DOX with a maximum loading 23 % ± 2.05. Preparation of Apt-PEG-DOX@GNP yielded uniform particles with an average diameter of 144.73 ± 11.29 nm. The Apt-PEG-DOX@GNP demonstrated iron-dependent release behaviors, wherein the cleavage of DFP−COOH-Cu(II) bonds decorating the silica nanoparticles occurred asynchronously, leading to the formation of new DFP−COOH-Fe(II) bonds for the subsequent release of DOX. The in vivo experiments revealed that the biocompatible nanocarriers displayed targeted toxicity towards C26 tumor-bearing BALB/c mice, resulting in minimal side effects. ConclusionOur prepared novel nanoplatforms showed promising potential for targeted treatment of colorectal cancer and precise control over the drug release.

Nonclinical Pharmacokinetics Study of OLX702A-075-16, N-Acetylgalactosamine Conjugated Asymmetric Small Interfering RNA (GalNAc-asiRNA).

In this study, the nonclinical pharmacokinetics of OLX702A-075-16, an RNA interference therapeutic currently in development, were investigated. OLX702A-075-16 is a novel N-acetylgalactosamine conjugated asymmetric small-interfering RNA (GalNAc-asiRNA) used for the treatment of an undisclosed liver disease. Its unique 16/21-mer asymmetric structure reduces nonspecific off-target effects without compromising efficacy. We investigated the plasma concentration, tissue distribution, metabolism, and renal excretion of OLX702A-075-16 following a subcutaneous administration in mice and rats. For bioanalysis, high-performance liquid chromatography with fluorescence detection was used. The results showed rapid clearance from plasma (0.5 to 1.5 hours of half-life) and predominant distribution to the liver and/or kidney. Less than 1% of the liver concentration of OLX702A-075-16 was detected in the other tissues. Metabolite profiling using liquid chromatography coupled with high-resolution mass spectrometry revealed that the intact duplex OLX702A-075-16 was the major compound in plasma. The GalNAc moiety was predominantly metabolized from the sense strand in the liver, with the unconjugated sense strand of OLX702A-075-16 accounting for more than 95% of the total exposure in the rat liver. Meanwhile, the antisense strand was metabolized by the sequential loss of nucleotides from the 3'-terminus by exonuclease, with the rat liver samples yielding the most diverse truncated forms of metabolites. Urinary excretion over 96 hours was less than 1% of the administered dose in rats. High plasma protein binding of OLX702A-075-16 likely inhibited its clearance through renal filtration. SIGNIFICANCE STATEMENT: This study presents the first comprehensive characterization of the in vivo pharmacokinetics of GalNAc-asiRNA. The pharmacokinetic insights gained from this research will aid in understanding toxicology and efficacy, optimizing delivery platforms, and improving the predictive power of preclinical species data for human applications.

An in situ bioadhesive foam as a large intestinal delivery platform for antibody fragment to treat inflammatory bowel disease

Biologics have been widely used as injectables in the treatment of inflammatory bowel disease (IBD). Different local treatment attempts have been developed in recent years. However, maintaining systemic levels of biologics is still crucial for achieving colitis remission. An equilibrium between systemic and local concentrations of biologics is therefore essential for treatment of colitis. Current formulations struggle to create optimal balance between drug concentrations in plasma and the colonic wall. Addressing this challenge, we developed a rectally delivered in situ foam that generates CO2via a reaction between potassium bicarbonate (PB) and citric acid (CA) without the aid of an external device. An anti-TNF-α antibody fragment (Fab) was loaded into the foam formulation, which promoted prolonged colon retention and improved Fab distribution up to proximal colon following rectal administration to mice. In addition, we observed increased plasma Fab concentrations in mice receiving the rectal Fab foam compared to a Fab solution. In a non-everted rat gut ex vivo model, a single exposure to the CO2-containing foam improved macromolecule transepithelial flux across colonic tissue by over ten-fold. Foam efficacy for Fab was investigated in a range of colitis mouse models, from acute to chronic. This non-invasive formulation platform demonstrates potential to overcome existing limitations in delivering biologics to inflamed colonic tissue.

Bio-inspired biorthogonal compartmental microparticles for tumor chemotherapy and photothermal therapy

Microcarrier is a promising drug delivery system demonstrating significant value in treating cancers. One of the main goals is to devise microcarriers with ingenious structures and functions to achieve better therapeutic efficacy in tumors. Here, inspired by the nucleus-cytoplasm structure of cells and the material exchange reaction between them, we develop a type of biorthogonal compartmental microparticles (BCMs) from microfluidics that can separately load and sequentially release cyclooctene-modified doxorubicin prodrug (TCO-DOX) and tetrazine-modified indocyanine green (Tz-ICG) for tumor therapy. The Tz-ICG works not only as an activator for TCO-DOX but also as a photothermal agent, allowing for the combination of bioorthogonal chemotherapy and photothermal therapy (PTT). Besides, the modification of DOX with cyclooctene significantly decreases the systemic toxicity of DOX. As a result, the developed BCMs demonstrate efficient in vitro tumor cell eradication and exhibit notable tumor growth inhibition with favorable safety. These findings illustrate that the formulated BCMs establish a platform for bioorthogonal prodrug activation and localized delivery, holding significant potential for cancer therapy and related applications.Graphical

Influence of co-solvents on properties of terpene-based eutectic mixtures: Implications for skin delivery

Terpene-based eutectic mixtures (EMs) are attractive platforms for transdermal delivery due to their solubilizing potential and ability to alter the barrier function of the stratum corneum (SC). Despite this, little is known about the effect of diluting EMs with co-solvents (CSs) on their solubility- and permeation-enhancing properties. Furthermore, insufficient attention has been paid to comparing these platforms with traditional solvents, such as propylene glycol (PG) or ethanol (EtOH). To address this gap, the present study investigates the impact of the CS content in EM:CS blends on the transdermal delivery of clotrimazole (CLOT). Two CSs, PG and EtOH, and two terpene-based EMs, menthol:thymol and thymol:β-citronellol, were used. Each of the EMs was investigated at two different molar ratios between the terpenes, with one being their eutectic point, to explore its potential benefit for skin permeation. At each step, properties of the blends were compared with those of pure CSs. The EM:CS blends showed a better solubilizing potential for CLOT than EMs or CSs on their own. A higher content of CSs in the blends resulted in a higher skin permeation and retention of CLOT, and a lower degree of disarrangement of the SC structure. Furthermore, the blends of EMs at their EPs led to overall poorer permeation profiles, implying that the permeation rate is more affected by the properties of the individual terpenes than by the specific ratio at the eutectic point between them. In conclusion, addition of CSs to the EMs promotes permeation and retention of CLOT, while reducing the skin impairment caused by the terpenes.

Stimuli-Responsive Covalent Organic Frameworks for Cancer Therapy.

Chemotherapy as a common anticancer therapeutic modality is often challenged by various obstacles such as poor stability, low solubility, and severe side effects of chemotherapeutic agents as well as multidrug resistance of cancerous cells. Nanoparticles in the role of carriers for chemotherapeutic drugs and platforms for combining different therapeutic approaches have effectively participated in overcoming such drawbacks. In particular, nanoparticles able to induce their therapeutic effect in response to specific stimuli like tumor microenvironment characteristics (e.g., hypoxia, acidic pH, high levels of glutathione, and overexpressed hydrogen peroxide) or extrinsic stimulus of laser light bring about more precise and selective treatments. Among them, nanostructures of covalent organic frameworks (COFs) have drawn great interest in biomedical fields during recent years. Possessing large surface area, high porosity, structural stability, and customizable architecture, these biocompatible porous crystalline polymers properly translate to promising platforms for drug delivery and induction of combination therapies. With the focus on stimuli-responsive characteristics of nanoscale COFs, this study aims to propose an overview of their potentiality in cancer treatment on the basis of chemotherapy alone or in combination with sonodynamic, chemodynamic, photodynamic, and photothermal therapies.

The electro-responsive nanoliposome as an on-demand drug delivery platform for epilepsy treatment

Nano-based drug delivery systems are regarded as a promising tool for efficient epilepsy treatment and seizure medication with the least general side effects and socioeconomic challenges. In the current study, we have designed a smart nanoscale drug delivery platform and applied it in the kindling model of epilepsy that is triggered rapidly by epileptic discharges and releases anticonvulsant drugs in situ, such as carbamazepine (CBZ). The CBZ-loaded electroactive ferrocene nanoliposomes had an average diameter of 100.6 nm, a surface charge of −7.08 mV, and high drug encapsulation efficiency (85.4 %). A significant increase in liposome size was observed in response to direct current (50–500 μA) application. This liposome-based drug delivery system can release CBZ at a fast rate in response to both direct current and pulsatile electrical stimulation in vitro. The CBZ-liposome can release the anticonvulsant drug upon epileptiform activity in the kindled rat model and can decline electrographic and behavioral seizure activity in response to electrical stimulation of the hippocampus with an initially subconvulsive current. With satisfactory biosafety results, this “smart” nanocarrier has promising potential as an effective and safe drug delivery system to improve the therapeutic index of antiepileptic drugs.

Stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and verteporfin for glioblastoma therapy

BackgroundThe Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree.ResultsIn this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects.ConclusionSpecific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.

An enhanced intracellular delivery platform based on a distant diphtheria toxin homolog that evades pre-existing antitoxin antibodies

Targeted intracellular delivery of therapeutic proteins remains a significant unmet challenge in biotechnology. A promising approach is to leverage the intrinsic capabilities of bacterial toxins like diphtheria toxin (DT) to deliver a potent cytotoxic enzyme into cells with an associated membrane translocation moiety. Despite showing promising clinical efficacy, widespread deployment of DT-based therapeutics is complicated by the prevalence of pre-existing antibodies in the general population arising from childhood DT toxoid vaccinations, which impact the exposure, efficacy, and safety of these potent molecules. Here, we describe the discovery and characterization of a distant DT homolog from the ancient reptile pathogen Austwickia chelonae that we have dubbed chelona toxin (ACT). We show that ACT is comparable to DT structure and function in all respects except that it is not recognized by pre-existing anti-DT antibodies circulating in human sera. Furthermore, we demonstrate that ACT delivers heterologous therapeutic cargos into target cells more efficiently than DT. Our findings highlight ACT as a promising new chassis for building next-generation immunotoxins and targeted delivery platforms with improved pharmacokinetic and pharmacodynamic properties.

Nanotechnology-Based Approaches for Nose-to-Brain Drug Delivery in Neurodegenerative Diseases

: Drug delivery to the brain is a challenging task as many drugs do not cross the blood-brain barrier (BBB). As a result, designing strategies to target drugs to the brain requires significant effort. However, recent research has focused on the administration of drugs through the nose to the brain, a noninvasive way to bypass the BBB and deliver therapeutic molecules directly to the brain. Nose-to-brain drug delivery is a promising approach that allows for the direct transportation of therapeutic molecules to the brain while increasing drug concentration in the brain. This approach has gained considerable attention due to its non-invasive nature, which makes it feasible, reliable, and efficient. One promising approach for nose-to-brain drug delivery is the use of nanoparticles as a platform for drug and gene delivery. Nanoparticles offer several advantages, including the ability to protect therapeutic drugs from degradation and increase the efficacy of drug delivery due to their unique size, shape, and surface features. Nanoparticles can also be engineered to target specific cells or tissues, enabling more precise drug delivery to the brain. The use of nanoparticles for nose-to-brain drug delivery has been extensively studied, and recent developments have shown promising results. In addition, patents relating to medication targeting via the nasal route have been developed. These patents cover various aspects of drug delivery, including the use of different types of nanoparticles, methods for producing nanoparticles, and methods for delivering nanoparticles to the brain.

Surgery Combined with Local Implantation of Doxorubicin-Functionalized Hydroxyapatite Halts Tumor Growth and Prevents Bone Destruction in an Aggressive Osteosarcoma.

Osteosarcoma treatment comprises pre-surgical chemotherapy followed by radical surgery and further chemotherapy cycles, but the prognosis has been far from satisfactory. No new drugs or treatment modalities have been developed for clinical use in the last four decades. We describe a nano-hydroxyapatite (HA)-based local drug delivery platform for the delivery of doxorubicin (DOX), a cornerstone drug in osteosarcoma treatment. The efficacy of the developed drug delivery system was evaluated in an orthotopic human osteosarcoma xenograft in the proximal tibia of mice. After tumor development, the tumor was surgically resected and the void filled with the following: (1) No treatment (G1); (2) nHA only (G2); (3) DOX-loaded nHA (G3). In-vivo tumor response was assessed by evaluating the tumor-induced osteolysis at 2 weeks using micro-CT followed by in-vivo PET-CT at 3 weeks and ex-vivo micro-CT and histology. Micro-CT imaging revealed complete destruction of the tibial metaphysis in groups G1 and G2, while the metaphysis was protected from osteolysis in G3. PET-CT imaging using 18F-FDG revealed high metabolic activity in the tumors in G1 and G2, which was significantly reduced in G3. Using histology, we were able to verify that local DOX delivery reduced the bone destruction and the tumor burden compared with G1 and G2. No off-target toxicity in the vital organs could be observed in any of the treatment groups histologically. This study describes a novel local drug adjuvant delivery approach that could potentially improve the prognosis for patients responding poorly to the current osteosarcoma treatment.

A location and capacity-allocation game model for two competing online delivery platforms seeking new customers

A location and capacity-allocation game model for two competing online delivery platforms seeking new customers

The Impact of Food Delivery Riders’ Perception of Fairness on Organizational Identification in the Digital Economy: Based on the Intermediary Perspective of Organizational Trust in the Context of Digital Technology

With the rapid rise in the gig economy driven by advancements in digital technology and financial technology, this study focuses on the work experiences and psychological perceptions of food delivery riders in platform-based employment. This study used a sample of food delivery riders from 19 cities in China (such as Shanghai, Beijing, Guangzhou, etc.) and multiple delivery platforms (such as Meituan, Ele.me) to collect data through a combination of online and offline questionnaires. The impact relationship between perceived fairness, organizational trust, and organizational identity of food delivery riders was examined through factor analysis, structural equation modeling, and mediation effect modeling. The results of the survey and statistical analysis indicate that fairness perception and its dimensions (distributive fairness, procedural fairness, and interactional fairness) significantly influence riders’ organizational identification, with organizational trust serving as a critical mediating factor. The integration of digital technology has substantially enhanced the operational efficiency of platform-based employment by enabling real-time tracking, transparent communication, and data-driven decision-making. Innovations in financial technology, such as digital payment systems and financial management tools, offer riders safer and more convenient compensation methods, thereby contributing to their financial stability and fostering trust in the platform. The establishment of trust alleviates the riders’ concerns regarding compensation stability and bolsters their optimistic attitudes toward accessing platform resources and meeting their needs. This study provides significant insights and recommendations for leveraging digital technology and financial technology to improve the relationship and operational efficiency between riders and platform enterprises.

Lipid polymer hybrid nanoparticles against lung cancer and their application as inhalable formulation.

Lung cancer is a leading cause of global cancer mortality, often treated with chemotherapeutic agents. However, conventional approaches such as oral or intravenous administration of drugs yield low bioavailability and adverse effects. Nanotechnology has unlocked new gateways for delivering medicine to their target sites. Lipid-polymer hybrid nanoparticles (LPHNPs) are one of the nano-scaled delivery platforms that have been studied to exploit advantages of liposomes and polymers, enhancing stability, drug loading, biocompatibility and controlled release. Pulmonary administration of drug-loaded LPHNPs enables direct lung deposition, rapid onset of action and heightened efficacy at low doses of drugs. In this manuscript, we will review the potential of LPHNPs in management of lung cancer through pulmonary administration.

NDV targets the invasion pathway in malaria parasite through cell surface sialic acid interaction.

Merozoites utilize sialic acids on the red blood cell (RBC) cell surface to rapidly adhere to and invade the RBCs. Newcastle disease virus (NDV) displays a strong affinity toward membrane-bound sialic acids. Incubation of NDV with the malaria parasites dose-dependently reduces its cellular viability. The antiplasmodial activity of NDV is specific, as incubation with Japanese encephalitis virus, duck enteritis virus, infectious bronchitis virus, and influenza virus did not affect the parasite propagation. Interestingly, NDV is reducing more than 80% invasion when RBCs are pretreated with the virus. Removal of the RBC surface proteins or the NDV coat proteins results in disruption of the virus binding to RBC. It suggests the involvement of specific protein: ligand interaction in virus binding. We established that the virus engages with the parasitized RBCs (PRBCs) through its hemagglutinin neuraminidase (HN) protein by recognizing sialic acid-containing glycoproteins on the cell surface. Blocking of the HN protein with free sialic acid or anti-HN antibodies abolished the virus binding as well as its ability to reduce parasite growth. Interestingly, the purified HN from the virus alone could inhibit the parasite's growth in a dose-dependent manner. NDV binds strongly to knobless murine parasite strain Plasmodium yoelii and restricted the parasite growth in mice. Furthermore, the virus was found to preferentially target the PRBCs compared to normal erythrocytes. Immunolocalization studies reveal that NDV is localized on the plasma membrane as well as weakly inside the PRBC. NDV causes neither any infection nor aggregation of the human RBCs. Our findings suggest that NDV is a potential candidate for developing targeted drug delivery platforms for the Plasmodium-infected RBCs.

Unlocking the Potential of Camel Milk-Derived Exosomes as Novel Delivery Systems: Enhanced Bioavailability of ARV-825 PROTAC for Cancer Therapy.

This study investigates the use of camel milk-derived exosomes (CMEs) as carriers for ARV-825, an anticancer agent targeting bromodomain-containing protein 4 (BRD4), in oral chemotherapy. CMEs were isolated and characterized, and ARV-825-loaded CME formulations were prepared and evaluated through various in vitro and in vivo tests. The ARV-825-CME formulation exhibited an entrapment efficiency of 42.75 ± 5.05%, a particle size of 136.8 ± 1.94 nm, and a zeta potential of -32.75 ± 0.70 mV, ensuring stability and sustained drug release. In vitro studies showed a 5.4-fold enhancement in drug release kinetics compared to the free ARV-825 solution. Permeability studies indicated a 3.2-fold increase in apparent permeability, suggesting improved cellular uptake. Cytotoxicity assays demonstrated potent anticancer activity, with IC50 values decreasing by 1.5 to 2-fold in cancer cell lines SF8628 DIPG and H1975R (resistant to Osimertinib). In vivo pharmacokinetic studies in Sprague-Dawley rats revealed superior systemic absorption and bioavailability of ARV-825 from CMEs, with a 2.55-fold increase in plasma concentration and a 5.56-fold increase in AUC. Distribution studies confirmed absorption through the ileum. This research highlights the potential of CMEs as a promising delivery platform for ARV-825, enhancing its therapeutic efficacy and offering a novel approach to cancer treatment.

Coarse-Grained Simulation of mRNA-Loaded Lipid Nanoparticle Self-Assembly.

Ionizable lipid-containing lipid nanoparticles (LNPs) have enabled the delivery of RNA for a range of therapeutic applications. In order to optimize safe, targeted, and effective LNP-based RNA delivery platforms, an understanding of the role of composition and pH in their structural properties and self-assembly is crucial, yet there have been few computational studies of such phenomena. Here we present a coarse-grained model of ionizable lipid and mRNA-containing LNPs. Our model allows access to the large length- and time-scales necessary for LNP self-assembly and is mapped and parametrized with reference to all-atom structures and simulations of the corresponding components at compositions typical of LNPs used for mRNA delivery. Our simulations reveal insights into the dynamics of self-assembly of such mRNA-encapsulating LNPs, as well as the subsequent pH change-driven LNP morphology and release of mRNA.

Enhancing Dissolution and Bioavailability: A Review on Co-Processed Superdisintegrants in Pharmaceutical Formulations

Co-processed superdisintegrants have emerged as key excipients in pharmaceutical formulation development, offering solutions to challenges related to poor solubility, bioavailability, and patient compliance. This comprehensive review article provides an in-depth analysis of the principles, mechanisms, manufacturing techniques, and applications of co-processed superdisintegrants in drug delivery systems. The review highlights the role of co-processed excipients in enhancing dissolution kinetics, improving formulation efficiency, and enabling innovative drug delivery platforms such as personalized medicine and combination therapies. Regulatory considerations, quality standards, and future directions for research and innovation in this field are also discussed. Through a synthesis of current literature and insights into emerging trends, this review aims to provide researchers, formulation scientists, and pharmaceutical professionals with a comprehensive understanding of the potential and challenges associated with co-processed superdisintegrants in pharmaceutical formulations. Ultimately, the integration of co-processed excipients into formulation development holds promise for advancing drug delivery technology, improving therapeutic outcomes, and addressing unmet medical needs in patient care. Keywords: Co-processed superdisintegrants, Dissolution enhancement, Bioavailability, Pharmaceutical formulations, Drug delivery systems, Excipients, Formulation optimization, Manufacturing techniques, Regulatory considerations, Future directions

Adeno-associated virus-based gene therapy treats inflammatory kidney disease in mice.

Adeno-associated virus (AAV) is a promising in vivo gene delivery platform showing advantages in delivering therapeutic molecules to difficult or undruggable cells. However, natural AAV serotypes have insufficient transduction specificity and efficiency in kidney cells. Here, we developed an evolution-directed selection protocol for renal glomeruli and identified what we believe to be a new vector termed AAV2-GEC that specifically and efficiently targets the glomerular endothelial cells (GEC) after systemic administration and maintains robust GEC tropism in healthy and diseased rodents. AAV2-GEC-mediated delivery of IdeS, a bacterial antibody-cleaving proteinase, provided sustained clearance of kidney-bound antibodies and successfully treated antiglomerular basement membrane glomerulonephritis in mice. Taken together, this study showcases the potential of AAV as a gene delivery platform for challenging cell types. The development of AAV2-GEC and its successful application in the treatment of antibody-mediated kidney disease represents a significant step forward and opens up promising avenues for kidney medicine.