Chemical synthesis of super messenger RNA medicine.

Messenger RNAmRNAmedicine was urgently approved in 2020 as a vaccine for COVID-19 . However, current mRNA therapeutics are not fully established, with challenges remaining in translation efficiency and drug delivery system. Therefore, further research is needed to adapt mRNA therapeutics to other diseases. Furthermore, the preparation of mRNA drugs is time-consuming and costly because of the biological methods used. Our laboratory has been working on chemical methods to solve these issues. In this paper, we introduce chemical modifications and novel capping reactions as a method to improve the translation efficiency of mRNA and the introduction of disulfide modification to oligonucleotide therapeutics as an effort on the drug delivery system.Copyright © 2023, Japan Society of Drug Delivery System. All rights reserved.

Chemical synthesis of super messenger RNA medicine

Messenger RNA(mRNA)medicine was urgently approved in 2020 as a vaccine for COVID-19 . However, current mRNA therapeutics are not fully established, with challenges remaining in translation efficiency and drug delivery system. Therefore, further research is needed to adapt mRNA therapeutics to other diseases. Furthermore, the preparation of mRNA drugs is time-consuming and costly because of the biological methods used. Our laboratory has been working on chemical methods to solve these issues. In this paper, we introduce chemical modifications and novel capping reactions as a method to improve the translation efficiency of mRNA and the introduction of disulfide modification to oligonucleotide therapeutics as an effort on the drug delivery system.Copyright © 2023, Japan Society of Drug Delivery System. All rights reserved.

Synthesis of 6″-Modified Kanamycin A Derivatives and Evaluation of Their Antibacterial Properties.

Aminoglycosides are one of the first classes of antibiotics to have been used clinically, and they are still being used today. They have a broad spectrum of antimicrobial activity, making them effective against many different types of bacteria. Despite their long history of use, aminoglycosides are still considered promising scaffolds for the development of new antibacterial agents, particularly as bacteria continue to develop resistances to existing antibiotics. We have synthesized a series of 6″-deoxykanamycin A analogues with additional protonatable groups (amino-, guanidino or pyridinium) and tested their biological activities. For the first time we have demonstrated the ability of the tetra-N-protected-6″-O-(2,4,6-triisopropylbenzenesulfonyl)kanamycin A to interact with a weak nucleophile, pyridine, resulting in the formation of the corresponding pyridinium derivative. Introducing small diamino-substituents at the 6″-position of kanamycin A did not significantly alter the antibacterial activity of the parent antibiotic, but further modification by acylation resulted in a complete loss of the antibacterial activity. However, introducing a guanidine residue led to a compound with improved activity against S. aureus. Moreover, most of the obtained 6″-modified kanamycin A derivatives were less influenced by the resistant mechanism associated with mutations of the elongation factor G than the parent kanamycin A. This suggests that modifying the 6″-position of kanamycin A with protonatable groups is a promising direction for the further development of new antibacterial agents with reduced resistances.

Functionalized starch for formulation of graphitic carbon nanodots as viricidal/anticancer laborers

Biocompatibility of carbon nanodots (CNDs) ingrained from biopolymers are considered as prerequisite characters for their successive exploitation in different biomedical purposes. CNDs are known to be categorized to carbogenic nanodots (CgNDs) and graphitic nanodots (GNDs). The point of novelty in the current approach is to study the effect of chemical medication for starch before and after its functionalization with glucose, to ingrain carbon nanodots, that were sequentially applicable as viricidal and anticancer laborers. The represented data revealed that, CgNDs were nucleated from alkali-hydrolyzed starch exhibited with particle size of 4.8 ± 1.8 nm, whereas, glucose-functionalized starch was successfully exploited for ingraining of GNDs with particle size of 3.1 ± 1.3 nm. The viricidal action of the prepared CgNDs and GNDs against Low Pathogenic Coronavirus (229E) was estimated via CPE-inhibition Assay and the obtained IC50 was 61.2 and 29.6 mg/mL for CgNDs and GNDs, respectively. The synthesized CgNDs and GNDs were tested against human non-small cell lung cancer cell line (NSCLC, A549) via Sulforhodamine B (SRB) assay and the estimated IC50 was 356.5 and 220.3 μg/mL in case of CgNDs and GNDs, respectively. The obtained data approved the seniority of GNDs over CgNDs to be applicable as antiviral and antitumor laborers. © 2022 Elsevier Ltd

A comparative performance of antibacterial effectiveness of copper and silver coated textiles

During current COVID-19 crises, the antimicrobial textiles primarily those utilized in hospital by doctors and paramedical staff have become increasingly important. Thus, there is an unmet requirement to develop antimicrobial textiles for infection control and hygiene practices. Metallic nanoparticles exhibit great effectiveness towards resistant microbial species making them a potential solution to the increasing antibiotic resistance. Due to this, nanoparticles particularly copper and silver have become most prevalent forms of antibacterial finishing agents for the development of antimicrobial textiles. This review is mainly focused on the significance of copper and silver nanoparticles for the development of antimicrobial textiles. The comparative analysis of the antibacterial effectiveness of copper and silver nanoparticles as well as the possible physical and chemical interactions responsible for their antibacterial action are explained. The negative impact of pathogenic microbes on textiles and possible interactions of antimicrobial agents with microbes have also been highlighted. The significance of nanotechnology for the development of antimicrobial textiles and their applications in medical textiles domain have also been discussed. Various green synthesis and chemical methods used for the synthesis of Ag and Cu nanoparticles and their application on textile substrates to impart antimicrobial functionality have also been discussed. The various qualitative and quantitative standard testing protocols utilised for the antimicrobial characterization of textiles have also discussed in this review. The developed Cu and Ag coated textiles could be effectively applied in the field of hospital textiles for the preparation of antibacterial scrub suits, surgical gowns, panel covers, protective clothing, bedding textiles, coveralls, wound dressings, table covers, curtains, and chair covers etc. © The Author(s) 2022.

Precision Nanomedicine Targeting Novel Endothelial Mechano-Sensing Mechanisms and Treating Vascular Complications in vivo

Introduction: Endothelial mechano-transduction mechanisms are instrumental to vascular health and disease. Novel strategies targeting disease-causing mechano-sensitive pathways in dysfunctional endothelial cells could revolutionize future cardiovascular therapeutics. Vascular complications such as atherosclerosis and stenosis preferentially develop at arterial curvatures and bifurcations where endothelial cells are activated by local disturbed blood flow, leading to peripheral artery disease, carotid artery disease and ischemic stroke. Hypothesis: Current vascular therapies mainly target systematic risk factors (e.g. hypercholesterolemia and hypertension) but not the diseased vasculature, distinct molecular/cellular signatures of which can be targeted by innovated precision nanomedicine approaches. Method(s): We first elucidated novel mechano-sensitive molecular mechanisms in endothelium activated by disturbed flow (DF) and then engineered rationally-designed nano-materials with purposed-constructed functionalities to deliver therapeutic nucleotides to DF-activated endothelial cells. Result(s): Our results elucidated previously unrecognized endothelial mechano-sensitive pathways in endothelial activation, with emphasis upon cellular metabolism (DF-induced glycolysis), human genetic variants (DF-induced suppression of PLPP3, a CAD GWAS gene), miRNA, protein stability (DF-induced NOS3 protein degradation via TXNDC5) and mRNA chemical modification/epitranscriptome (DF-induced suppression of m7G). VCAM1-targeting nanoparticles were engineered to deliver therapeutic nucleotides such as mRNA, miRNA inhibitor, or CRISPR/Cas9 constructs specifically to inflamed endothelial cells to intervene aforementioned mechano-sensitive pathways, effectively reducing atherosclerosis and stenosis in mice. Similar approaches were very effective to promote endothelial health and lessen acute respiratory distress syndrome (ARDS) in mice induced by influenza or SARS-CoV-2 viruses. Conclusion(s): These results elucidate novel endothelial mechano-sensing mechanisms and provide a proof of concept of innovative targeted nanomedicine approaches, addressing an unmet medical need in vascular therapies.

Functionalized starch for formulation of graphitic carbon nanodots as viricidal/anticancer laborers

Biocompatibility of carbon nanodots (CNDs) ingrained from biopolymers are considered as prerequisite characters for their successive exploitation in different biomedical purposes. CNDs are known to be categorized to carbogenic nanodots (CgNDs) and graphitic nanodots (GNDs). The point of novelty in the current approach is to study the effect of chemical medication for starch before and after its functionalization with glucose, to ingrain carbon nanodots, that were sequentially applicable as viricidal and anticancer laborers. The represented data revealed that, CgNDs were nucleated from alkali-hydrolyzed starch exhibited with particle size of 4.8 ± 1.8 nm, whereas, glucose-functionalized starch was successfully exploited for ingraining of GNDs with particle size of 3.1 ± 1.3 nm. The viricidal action of the prepared CgNDs and GNDs against Low Pathogenic Coronavirus (229E) was estimated via CPE-inhibition Assay and the obtained IC50 was 61.2 and 29.6 mg/mL for CgNDs and GNDs, respectively. The synthesized CgNDs and GNDs were tested against human non-small cell lung cancer cell line (NSCLC, A549) via Sulforhodamine B (SRB) assay and the estimated IC50 was 356.5 and 220.3 μg/mL in case of CgNDs and GNDs, respectively. The obtained data approved the seniority of GNDs over CgNDs to be applicable as antiviral and antitumor laborers.

Research advances in the role of RNA m5C in viral replication

It is well-known that RNA is the target of numerous chemical modifications which currently amount to over a hundred. Among them, 5-methylcytosine (m5C) is a prevalent RNA modification in multiple eukaryotic RNA species, such as messenger RNAs (mRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), vault RNAs (vtRNAs), long non-coding RNAs (lncRNAs) and enhancer RNAs (eRNAs). In recent years, several techniques for detecting m5C have been developed, including UPLC-MS/MS, m5C-MeRIP-seq, PA-m5C-seq, RNA-BisSeq and nanopore sequencing. The rapid development of these high-throughput techniques sharply facilitates the in-depth studies of the biological functions of m5C. The m5C modification is enriched around start codon along mRNAs and conserved in tRNAs and rRNAs. It is a reversible RNA modification catalyzed by methyltransferases (NSUN, DNMT, and TRDMT family members) and removed by demethylases (TET family members and ALKBH1). The m5C modification can be recognized by a set of RNA-binding proteins (YBX family members, ALYREF and FMRP) and is widely involved in the regulation of RNA metabolic processes, including nuclear export, stability and translation. In addition, the dysregulation of m5C modification is closely related with the defect of DNA repair, cell proliferation, embryonic development and stem cell differentiation. Viruses are infectious agents that rely on host cells for replication. They have evolved numerous strategies to shape the cellular biosynthesis and metabolism machinery of hosts to complete their life cycle and propagate. One strategy is to modify viral RNAs using host m5C RNA methyltransferases (NSUN1, NSUN2, NSUN5 and DNMT2), and thus directly regulates their transcription, splicing and translation. So far, combined with the high-throughput techniques, some viral m5C landscapes have been precisely depicted, including human immunodeficiency virus type (HIV-1), murine leukemia virus (MLV), Epstein-Barr virus (EBV), and so on. Studies showed that the m5C level of retroviral mRNAs is much higher than cellular mRNAs, suggesting this modification can be a special marker for host cells to distinguish “self” and “non-self”. In addition, the m5C methylome of cellular RNAs is dynamically regulated under viral infection, leading to the suppression of host innate immunity. Therefore, it will be of great significance in the design and development of novel antiviral drugs by systemically understanding the molecular mechanisms of m5C modification in controlling viral replication and host innate immunity. In this review, the latest findings of m5C methyltransferases, demethylases, reader proteins and high-throughput sequencing techniques are presented. We discuss how m5C modification is catalyzed and recognized on viral RNAs of retrovirus, DNA virus, flavivirus and coronavirus. Furthermore, we summarize the roles of RNA m5C modification in viral replications and host innate immunity. This review will provide some valuable information for understanding the epigenetics in viral RNAs. © 2022 Chinese Academy of Sciences. All rights reserved.

Noncoding RNAs Emerging as Drugs or Drug Targets: Their Chemical Modification, Bio-Conjugation and Intracellular Regulation.

With the increasing understanding of various disease-related noncoding RNAs, ncRNAs are emerging as novel drugs and drug targets. Nucleic acid drugs based on different types of noncoding RNAs have been designed and tested. Chemical modification has been applied to noncoding RNAs such as siRNA or miRNA to increase the resistance to degradation with minimum influence on their biological function. Chemical biological methods have also been developed to regulate relevant noncoding RNAs in the occurrence of various diseases. New strategies such as designing ribonuclease targeting chimeras to degrade endogenous noncoding RNAs are emerging as promising approaches to regulate gene expressions, serving as next-generation drugs. This review summarized the current state of noncoding RNA-based theranostics, major chemical modifications of noncoding RNAs to develop nucleic acid drugs, conjugation of RNA with different functional biomolecules as well as design and screening of potential molecules to regulate the expression or activity of endogenous noncoding RNAs for drug development. Finally, strategies of improving the delivery of noncoding RNAs are discussed.

Chemically Modified Bovine ß-Lactoglobulin as a Broad-Spectrum Influenza Virus Entry Inhibitor with the Potential to Combat Influenza Outbreaks.

Frequent outbreaks of the highly pathogenic influenza A virus (AIV) infection, together with the lack of broad-spectrum influenza vaccines, call for the development of broad-spectrum prophylactic agents. Previously, 3-hydroxyphthalic anhydride-modified bovine ß-lactoglobulin (3HP-ß-LG) was proven to be effective against human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been used in the clinical control of cervical human papillomavirus (HPV) infections. Here, we show its efficacy in potently inhibiting infection by divergent influenza A and B viruses. Mechanistic studies suggest that 3HP-ß-LG binds, possibly through its negatively charged residues, to the receptor-binding domain in the hemagglutinin 1 (HA1) subunit in the HA of the influenza virus, thus inhibiting the attachment of the HA to sialic acid on host cells. The intranasal administration of 3HP-ß-LG led to the protection of mice against challenges by influenza A(H1N1)/PR8, A(H3N2), and A(H7N9) viruses. Furthermore, 3HP-ß-LG is highly stable when stored at 50 °C for 30 days and it shows excellent safety in vitro and in vivo. Collectively, our findings suggest that 3HP-ß-LG could be successfully repurposed as an intranasal prophylactic agent to prevent influenza virus infections during influenza outbreaks.

Advances and applications of dextran-based nanomaterials targeting inflammatory respiratory diseases

Dextran, a hydrophilic polysaccharide consists essentially of α-1,6 linked glucopyranoside residues that form the parent chain, along with α-1,2/3/4 linked residues that constitute its side chain. A considerable biocompatibility, stability under mildly acidic and basic conditions, solubility in water, non-immunogenicity, and presence of chemically modifiable –OH groups make dextran an ideal candidate for development of drug delivery vehicles and excipients. The presence of α-1,6 linkages in the parent chain provides enhanced chain mobility that determines the aqueous solubility of dextran, while its metabolism by the digestive enzymes to generate physiologically harmless degradation products validates its biocompatibility. Native dextran can be tuned for the development of pH-sensitive delivery systems by chemical modification that ensure an optimal drug concentration at the target site, and lowered dosing frequency that may ensure an overall improved patient compliance. The physicochemical properties of dextran can be changed by performing a chemical modification predominantly at the –OH group to obtain ester, ether, acetal, and dialdehyde of dextran. The review presented by us is a comprehensive account of the chemical modification strategies for native dextran and their clinical applications in containing pulmonary diseases. Furthermore, the presented review highlights the importance of nanomaterials derived from chemically modified dextran for the management of an optimal respiratory health by containing the inflammatory respiratory diseases.

Recent Advances in Chemically Modified Cellulose and Its Derivatives for Food Packaging Applications: A Review.

The application of cellulose in the food packaging field has gained increasing attention in recent years, driven by the desire for sustainable products. Cellulose can replace petroleum-based plastics because it can be converted to biodegradable and nontoxic polymers from sustainable natural resources. These products have increasingly been used as coatings, self-standing films, and paperboards in food packaging, owing to their promising mechanical and barrier properties. However, their utilization is limited because of the high hydrophilicity of cellulose. With the presence of a large quantity of functionalities within pristine cellulose and its derivatives, these building blocks provide a unique platform for chemical modification via covalent functionalization to introduce stable and permanent functionalities to cellulose. A primary aim of chemical attachment is to reduce the probability of component leaching in wet and softened conditions and to improve the aqueous, oil, water vapor, and oxygen barriers, thereby extending its specific use in the food packaging field. However, chemical modification may affect the desirable mechanical, thermal stabilities and biodegradability exhibited by pristine cellulose. This review exhaustively reports the research progress on cellulose chemical modification techniques and prospective applications of chemically modified cellulose for use in food packaging, including active packaging.

Specific Chemical Modification of Nanohole Edges in Membrane Graphene for Protein Binding

The vital role of biosensors in our lives is steadily increasing due to their wide range of applications. As part of our striving efforts to develop affordable and highly sensitive biosensing technologies, we present here the successful chemical modification of-and biological molecule attachment to-holes' edges formed in a sheet of graphene, named nanomembrane graphene (NMG). This work complements our previous work, which showed that NMG could be used as a mid-IR biosensor, in which it becomes essential to overcome the challenge of the specific chemical modification of the holes' edges. In this work, we formed the NMG on reduced graphene oxide (rGO) layer using Au nanoparticles (Au NPs) and nano-islands (Au NIs). The formation methods were optimized by applying a matrix of variable concentration, size, and deposition time, as well as by chemical modification of substrate. The optimum scenarios were defined as having an extremely thin rGO layer, Au NPs, or NIs with size and center-to-center distance of 20-35 and 40-60 nm, respectively, and to have weak interaction between the metal and the substrate to allow etching leading to the formation of holes. The chemical groups at the edges were investigated to define the best method to attach biological molecules to them. Finally, we demonstrated the successful measurement of the binding between SARS-CoV-2 spike protein and its antibody (ACE2);real-time binding measurements revealed an affinity constant of 0.93 × 109 M-1. We consider these results important as they demonstrate a new route to a low-cost and high-sensitivity biosensor. © 2022 American Chemical Society.

RNA binding to human METTL3-METTL14 restricts N6-deoxyadenosine methylation of DNA in vitro.

Methyltransferase like-3 (METTL3) and METTL14 complex transfers a methyl group from S-adenosyl-L-methionine to N6 amino group of adenosine bases in RNA (m6A) and DNA (m6dA). Emerging evidence highlights a role of METTL3-METTL14 in the chromatin context, especially in processes where DNA and RNA are held in close proximity. However, a mechanistic framework about specificity for substrate RNA/DNA and their interrelationship remain unclear. By systematically studying methylation activity and binding affinity to a number of DNA and RNA oligos with different propensities to form inter- or intra-molecular duplexes or single-stranded molecules in vitro, we uncover an inverse relationship for substrate binding and methylation and show that METTL3-METTL14 preferentially catalyzes the formation of m6dA in single-stranded DNA (ssDNA), despite weaker binding affinity to DNA. In contrast, it binds structured RNAs with high affinity, but methylates the target adenosine in RNA (m6A) much less efficiently than it does in ssDNA. We also show that METTL3-METTL14-mediated methylation of DNA is largely restricted by structured RNA elements prevalent in long noncoding and other cellular RNAs.

Cocaine induced organizing pneumonia

Case Report Cocaine is a potent natural stimulant that is widely used and is among the most common cause of acute drug related emergency department visits in the US. All different forms of cocaine can cause a variety of neuro-psychological, cardiovascular, and pulmonary injuries. Here we present a case of respiratory failure in patient with smokes cocaine in aluminum foil. Case A35-year-old morbidly obese female with no significant medical history except for daily cannabis uses and cocaine in the past who was admitted for progressive cough, dyspnea, and fever for 10 days. She smoked a different kind of marijuana recently. Family mentioned history of smoking cocaine using aluminum foil recently. no chest pain, rash, or joint pain, no recent travels. no family history of similar condition or autoimmune disease. vital signs fever of 38 C, O2 sat of 82% Room air, BP 162/ 90 mmHg, pulse of 124, RR of 34. Patient did have bilateral rales on respiratory examination. WBC was 25,000. ESR of 68, Pro-Cal 0.11. CT angiography of the chest showed bilateral ground glass opacities and patchy consolidation. Pan cultures, viral panel including Covid test, HIV, Autoimmune diseases, and Vasculitis work-up were negative. Bronchoalveolar lavage (BAL) revealed neutrophil 38, lymphocyte 39, Eosinophile 14, Cultures were negative. Urine toxicology screen was not done. Patient was started on broad spectrum antibiotic. Patient was intubated for Video assisted thoracoscopic surgery and biopsy but could not be done due to worsening respiratory status. Based on presentation and investigation findings, diagnosis of Cocaine induced Organizing pneumonia was made. Tapered steroid therapy was added with dexamethasone initial dose of 6 mg then methyleprednisolone 125 mg. patient recovered well, extubated on day 13, switched to oral prednisone and discharged home on room air. Discussion Cocaine is an alkaloid with anesthetic properties that is administered through different routes;inhaled, IV injections, or smoked after chemical modification 'crack'. It may be smoked through different types of pipes or mixed with cigarettes or marijuana. Mechanism of cocaine induced lung injury is thought to be due to inflammatory damage, thermal injury, direct cellular toxicity, barotrauma, or vasospastic ischemia. other possibility in our patient is Smoking in aluminum foil which has food oil substances, and none stick substances can make them toxic when inhaled. Cocaine induced organizing pneumonia with respiratory failure has been reported in young cocaine smokers. Organizing pneumonia BAL cell count has increase in lymphocyte (20-40), neutrophile (5-10) and eosinophile (5-25) with the level of lymphocyte being higher than eosinophile is typical but not diagnostic for COP. Conclusion Organizing pneumonia secondary to cocaine or aluminum foil with typical presentation, radiology imaging, BAL cell count findings and excluding other causes may be diagnosed without the need of lung biopsy.

A computational approach for designing novel SARS-CoV-2 Mproinhibitors: combined QSAR, molecular docking, and molecular dynamics simulation techniques

The normal expression of the main protease (Mpro) plays a vital role in the life cycle of coronavirus. Highly active inhibitors could inhibit the normal circulation of the main protease to achieve therapeutic effects as anti-coronavirus agents. In the present research, 48 peptide compounds with SARS-CoV Mproinhibition selected from the literature were used to establish robust Topomer CoMFA (q2= 0.743,r2= 0.938, andrpred2= 0.700) and HQSAR (q2= 0.774,r2= 0.955, andrpred2= 0.723) models. Structural modification information was used for designing new Mproinhibitors. The high contribution-value descriptor generated by Topomer CoMFA was used to screen for the fragments that possess significant inhibitory activities from the ZINC drug database, and 24 new compounds with predicted high inhibitory activity at nanomolar concentration were designed by combining the high contribution value fragments. The molecular docking results further justified that these potential inhibitors could form hydrogen bonds with the residues of CYS145, GLN189, GLU166, HIS163, and GLY143 of target Mpro, which well explains their strong inhibitory effects. The molecular dynamics simulation results indicated that four highly active compounds could stably bond with SARS-CoV-2 Mproand might be promising anti-SARS-CoV-2 Mprocandidates. Finally, all the newly designed compounds showed premium ADMET properties as per the predictions by the server in the public domain. This research work not only provides robust QSAR models as valuable screening tools for future anti-coronavirus drug development but also renders the newly designed SARS-CoV-2 Mproinhibitors with activity at nanomolar concentration, which can be used for further characterization to obtain novel anti-coronavirus drugs for both SARS-CoV and SARS-CoV-2.

The development and improvement of ribonucleic acid therapy strategies.

The biological understanding of RNA has evolved since the discovery of catalytic RNAs in the early 1980s and the establishment of RNA interference (RNAi) in the 1990s. RNA is no longer seen as the simple mid-product between transcription and translation but as potential molecules to be developed as RNA therapeutic drugs. RNA-based therapeutic drugs have gained recognition because of their ability to regulate gene expression and perform cellular functions. Various nucleobase, backbone, and sugar-modified oligonucleotides have been synthesized, as natural oligonucleotides have some limitations such as poor low nuclease resistance, binding affinity, poor cellular uptake, and toxicity, which affect their use as RNA therapeutic drugs. In this review, we briefly discuss different RNA therapeutic drugs and their internal connections, including antisense oligonucleotides, small interfering RNAs (siRNAs) and microRNAs (miRNAs), aptamers, small activating RNAs (saRNAs), and RNA vaccines. We also discuss the important roles of RNA vaccines and their use in the fight against COVID-19. In addition, various chemical modifications and delivery systems used to improve the performance of RNA therapeutic drugs and overcome their limitations are discussed.

Genetic and Chemical Capsid Modifications of Adenovirus Vectors to Modulate Vector-Host Interactions.

Adenovirus-based vectors are playing an important role as efficacious genetic vaccines to fight the current COVID-19 pandemic. Furthermore, they have an enormous potential as oncolytic vectors for virotherapy and as vectors for classic gene therapy. However, numerous vector-host interactions on a cellular and noncellular level, including specific components of the immune system, must be modulated in order to generate safe and efficacious vectors for virotherapy or classic gene therapy. Importantly, the current widespread use of Ad vectors as vaccines against COVID-19 will induce antivector immunity in many humans. This requires the development of strategies and techniques to enable Ad-based vectors to evade pre-existing immunity. In this review article, we discuss the current status of genetic and chemical capsid modifications as means to modulate the vector-host interactions of Ad-based vectors.