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Since the first use of vaccine tell the last COVID-19 pandemic caused by spread of SARS-CoV-2 worldwide, the use of advanced biotechnological techniques has accelerated the development of different types and methods for immunization. The last pandemic showed that the nucleic acid-based vaccine, especially mRNA, has an advantage in terms of development time; however, it showed a very critical drawback namely, the higher costs when compared to other strategies, and its inability to protect against new variants. This showed the need of more improvement to reach a better delivery and efficacy. In this review we will describe different vaccine delivery systems including, the most used viral vector, and also variable strategies for delivering of nucleic acid-based vaccines especially lipid-based nanoparticles formulation, polymersomes, electroporation and also the new powerful tools for the delivery of mRNA, which is based on the use of cell-penetrating peptides (CPPs). Additionally, we will also discuss the main challenges associated with each system. Finlay, the efficacy and safety of the vaccines depends not only on the formulations and delivery systems, but also the dosage and route of administration are also important players, therefore we will see the different routes for the vaccine administration including traditionally routes (intramuscular, Transdermal, subcutaneous), oral inhalation or via nasal mucosa, and will describe the advantages and disadvantage of each administration route.

Graft versus host disease (GVHD) remains the major cause of morbidity and mortality after allogeneic stem cell transplantation, especially for intestinal GVHD, as steroid resistant GVHD results in high mortality. For this reason, new treatments of GVHD are needed. One approach is the reduction of pathogenic bacteria using anti-E. coli Immunoglobulin Yolk (IgY). In a haploidentical murine model, B6D2F1 mice conditioned with total body irradiation (TBI), received bone marrow cells (BM) and splenocytes (SC) from either syngeneic (Syn = B6D2F1) or allogeneic (Allo = C57BL/6) donors. Following this, animals received from day −2 until day +28 chow contained IgY or control chow. Thereafter the incidence and severity of aGVHD, the cytokines, chemokines, IDO1 and different pathogen-recognition receptors (PRR) were analyzed and compared to control animals (received chow without IgY). We found that animals receiving chow with IgY antibody showed reduced GVHD severity compared to control animals. On day28 after alloBMT, IDO, NOD2, TLR2, TLR4 and the inflammatory chemokine CCL3, were reduced in the colon and correlated with a significant decrease in E. coli bacteria. In summary chow containing chicken antibodies (IgY) improved GVHD via decrease in bacterial load of E coli conducting to reduction of pathogen receptors (NOD2, TLR2 and 4), IDO, chemokines and cytokines.

Background: Coronary artery disease (CAD) is one of the common genetic and clinical risk factors associated with cardiovascular and multifactorial disorder. ATP-binding cassette transporter A1 (ABCA1) gene plays an important role in lipid metabolism and in multiple studies associated with CAD. However, more studies are needed to identify the exact role of single nucleotide polymorphisms which may cause CAD. Objectives: The aim of this study is to investigate the genetic association of polymorphism g.1051G > A in the ABCA1 gene with CAD patients in the Saudi population. Methods: We included 315 confirmed CAD cases, and 205 non-CAD or control subjects in this case-control study. DNA isolation was carried out for all registered participants and the polymorphism g.1051G > A was genotyped with Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism analysis with EcoNI restriction enzyme. Results: Modifiable risk factors such as Body Mass Index, smoking and diabetes were strongly associated and non-modifiable risk factors such as hypertension (Systolic Blood Pressure and Diastolic Blood Pressure) and serum analysis such as Fasting Blood Glucose, Total cholesterol (TC), Triglyceride (TG) and LDL-c were significantly associated in CAD cases (p A polymorphism. Conclusion: The polymorphism g.1051G > A in the gene ABCA1 is closely associated with the existence of the CAD subjects. This polymorphism could also affect the serum levels of the lipid profile, suggesting a possible occurrence of CAD in the Saudi population.

Background: Eczema is also known as atopic dermatitis is well-known for the skin disease globally. In Saudi Arabia, exome sequencing studies have not been documented. The purpose of this study was to scrutinize the disease causing mutations in children affected with eczema with exome sequencing in the Saudi population. Methods: We recruited randomly three sporadic cases of children diagnosed with eczema and simultaneously, three more cases were adopted for control samples. Exome sequencing was carried out by applying a pipeline that captures all the variants of concern related to the samples by using the Ion torrent. Results: In this study, we have documented 49 variants, among which 37 variants were confirmed through eczema children and remaining 30 variants through control children. However, from the analysis of the 6 samples, we have identified rs10192157 (1646C > T; Thr549Ile), rs2899642 (27C > G; Asn9Lys), chr1:152127950 (1625 G > A; Gly542Asp) and chr1:152128041 (1534C > G; Gly512Arg) variants which are rarely linked to the disease eczema. In the rs10192157, we have documented these mutations in all three eczema children and one in the control; the rs2899642 mutation appeared in only a couple of eczema children, whereas the mutation in the chr1:152127950 regions appeared in only one eczema patient. However, the chr1:152128041 mutations appeared in only one case of eczema and also in two control children. Conclusion: Our study revealed four mutations which had not previously been connected with eczema within the database. However, the rs10192157 and rs2899642 mutations were documented with asthma disease. The remaining mutations such as chr1:152127950 and chr1:152128041 have not been reported anywhere else. This study recommends screening these 4 mutations in eczema cases and their relevant controls to confirm the prevalence in the Saudi population. It is recommended that future studies examine the 4 mutations in detail. Keywords: Eczema, Exome-sequencing, Mutation, Variants

Cancer may be difficult to target, however, if cancer targeted this provides the chance for a better and more effective treatment. Quantum dots (Qdots) coated vapreotide (VAP) as a somatostatin receptors (SSTRs) agonist can be efficient targeting issue since may reduce side effects and increase drug delivery to the target tissue. This study highlights the active targeting of cancer cells by cells imaging with improving the therapeutic outcomes. VAP was conjugated to Qdots using amine-to-sulfhydryl crosslinker. The synthesized Qdots-VAP was characterized by determination of size, measuring the zeta-potential and UV fluorometer. The cellular uptake was studied using different cell lines. Finally, the Qdots-VAP was injected into a rat model. The results showed a size of 479.8 ± 15 and 604.88 ± 17 nm for unmodified Qdots and Qdots-VAP respectively, while the zeta potential of particles went from negative to positive charge which proved the conjugation of VAP to Qdots. The fluorometer recorded a redshift for Qdots-VAP compared with unmodified Qdots. Moreover, cellular uptake exhibited high specific binding with cells which express SSTRs using confocal microscopy and flow cytometry (17.3 MFU comparing to 3.1 MFU of control, P

A targeted customized sequencing of genes implicated in autosomal recessive polycystic kidney disease (ARPKD) phenotype was performed to identify candidate variants using the Ion torrent PGM next-generation sequencing. The results identified four potential pathogenic variants in PKHD1 gene [c.4870C>T, p.(Arg1624Trp), c.5725C>T, p.(Arg1909Trp), c.1736C>T, p.(Thr579Met) and c.10628T>G, p.(Leu3543Trp)] among 12 out of 18 samples. However, one variant c.4870C>T, p.(Arg1624Trp) was common among eight patients. Some patient samples also showed few variants in autosomal dominant polycystic kidney disease (ADPKD) disease causing genes PKD1 and PKD2 such as c.12433G>A, p.(Val4145Ile) and c.1445T>G, p.(Phe482Cys), respectively. All causative variants were validated by capillary sequencing and confirmed the presence of a novel homozygous variant c.10628T>G, p.(Leu3543Trp) in a male proband. We have recently published the results of these studies (Edrees et al., 2016). Here we report for the first time the effect of the common mutation p.(Arg1624Trp) found in eight samples on the protein structure and function due to the specific amino acid changes of PKHD1 protein using molecular dynamics simulations. The computational approaches provide tool predict the phenotypic effect of variant on the structure and function of the altered protein. The structural analysis with the common mutation p.(Arg1624Trp) in the native and mutant modeled protein were also studied for solvent accessibility, secondary structure and stabilizing residues to find out the stability of the protein between wild type and mutant forms. Furthermore, comparative genomics and evolutionary analyses of variants observed in PKHD1, PKD1, and PKD2 genes were also performed in some mammalian species including human to understand the complexity of genomes among closely related mammalian species. Taken together, the results revealed that the evolutionary comparative analyses and characterization of PKHD1, PKD1, and PKD2 genes among various related and unrelated mammalian species will provide important insights into their evolutionary process and understanding for further disease characterization and management.