• Antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass that binds to exon 53 of dystrophin pre-mRNA. (medscape.com)
  • Casimersen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass. (medscape.com)
  • Antisense RNA (asRNA), also referred to as antisense transcript, natural antisense transcript (NAT) or antisense oligonucleotide, is a single stranded RNA that is complementary to a protein coding messenger RNA (mRNA) with which it hybridizes, and thereby blocks its translation into protein. (wikipedia.org)
  • The idea of asRNAs as drug targets started in 1978 when Zamecnik and Stephenson found an antisense oligonucleotide to the viral RNA of Rous scarcoma virus that was capable of inhibiting viral replication and protein synthesis. (wikipedia.org)
  • When annealed to a complementary DNA target strand, the antisense oligonucleotide effected alkylation of guanosine residues in proximity to the phenazine di-N-oxide prosthetic group. (elsevierpure.com)
  • the latter effected strand scission of the target DNA oligonucleotide. (elsevierpure.com)
  • Several parameters of DNA degradation were studied, including the effect on DNA degradation of chain length in the tether connecting the oligonucleotides and prosthetic group, the relative efficiencies of DNA cleavage when the prosthetic group was in the middle or at the end of the antisense oligonucleotide, and the effect of O 2 on DNA degradation. (elsevierpure.com)
  • Also studied was the actual chemistry of DNA oligonucleotide degradation and the ability of individual diastereomers of the modified oligonucleotides to mediate degradation of the target DNA. (elsevierpure.com)
  • We studied the growth inhibition of the malignant glioma cell lines using an antisense EGFR oligonucleotide (normal phosphodister oligonucleotide) enveloped with Lipofectin^R (BRL) and we could have a good result. (nii.ac.jp)
  • This time, we succeeded to develop the recombinant retro-virus vector expressiog EGFR antisense oligonucleotide, and we could inhibit the growth of the malignant glioma cell line using this retro-virus vector. (nii.ac.jp)
  • Because transcription factors (such as IRF4) are difficult to target with traditional small-molecule strategies, researchers from the University of California (UC) San Diego School of Medicine and Ionis Pharmaceuticals used an antisense oligonucleotide-based inhibitory platform to reduce the stability of IRF4 transcripts for the purpose of disrupting cancer metabolism. (scienceboard.net)
  • The researchers tested a panel of human-specific antisense oligonucleotide agents targeting IRF4 in vitro and profiled their effects on multiple myeloma cell viability and IRF4 expression to determine a candidate that selectively inhibits human IRF4. (scienceboard.net)
  • The left image represents a microscopic view of the bone marrow of a myeloma-bearing mouse treated with the control, and the right image represents the same for a myeloma-bearing mouse treated with the antisense oligonucleotide ION251. (scienceboard.net)
  • The current study describes the implementation of a hybridization liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform for the direct quantitation of antisense oligonucleotide (ASO) ƒ u . (aspetjournals.org)
  • Secarna Pharmaceuticals, an IZB-based biopharmaceutical company focusing on the discovery and development of next-generation antisense oligonucleotide (ASO) therapies to address challenging or previously undruggable targets via its LNAplus™ platform, announced the publication of striking new preclinical data demonstrating that bimodal ASOs can enable efficacious long-term antitumor immunity in tumor models compared to current immune checkpoint inhibitors. (izb-online.de)
  • In a study published January 20, 2021 in Cell Stem Cell , the team details their successes inhibiting IRF4 with an antisense oligonucleotide, an engineered piece of DNA specifically designed to bind the genetic material coding for IRF4, causing it to degrade. (scienceblog.com)
  • The oligonucleotide - an investigational antisense medicine developed by Ionis and known as ION251 - lowered disease burden, reduced myeloma stem cell abundance and increased survival of mice bearing human myeloma, according to preclinical study data. (scienceblog.com)
  • Limited success in clinical trials for oligonucleotide therapeutics and gene therapy restricts the growth of antisense oligonucleotide. (researchandmarkets.com)
  • Examples of these RNA therapies include antisense oligonucleotide (ASO), small interfering RNA (siRNA), and microRNA (miRNA) therapies. (medlineplus.gov)
  • Site-specific degradation of DNA was achieved by the use of DNA oligonucleotides covalently tethered to phenazine 5,10-di-N-oxide. (elsevierpure.com)
  • Nagai, K & Hecht, SM 1991, ' Site-specific DNA cleavage by antisense oligonucleotides covalently linked to phenazine Di-N-oxide ', Journal of Biological Chemistry , vol. 266, no. 35, pp. 23994-24002. (elsevierpure.com)
  • The market for small snippets of DNA, called Oligonucleotides, is growing into a market for Synthetic DNA where organisms, like algae, are "custom designed" to produce food and medicine while consuming few resources. (pharmiweb.com)
  • Unmodified RNA, RNA with modifications, chimeric oligonucleotides with mixed DNA and RNA bases, 2'-OMe-RNA, 2'-F-RNA, and other antisense RNAs are available at your specific request. (genscript.com)
  • Hand-entering DNA sequence into a computer -- be it for ordering oligonucleotides, editing sequence reads, &c. -- is an error-prone, tedious and slow fine-motor process. (halfbakery.com)
  • The antisense oligonucleotides dramatically reduced survival of multiple myeloma cells and decreased human IRF4 messenger RNA (mRNA) and protein expression, as well as lowered expression of the IRF4 target gene MYC. (scienceboard.net)
  • The researchers noted that one benefit of antisense oligonucleotides is that they can be delivered into cells by free update with natural endocytic mechanisms, which enables rapid gene expression modulation compared to alternative gene delivery strategies. (scienceboard.net)
  • Antisense oligonucleotides (ASOs), defined as short synthetic oligonucleotides with single-stranded sequences complementary to certain mRNA sites, have been under drug development for approximately 30 years, with the first FDA-approved drug, Fomivirsen, being approved in 1998 ( Stein and Castanotto, 2017 ). (aspetjournals.org)
  • More specifically, antisense oligonucleotides that are useful as reagents for target validation , or as drugs, are engineered molecules that differ from natural RNA but that have a base sequence that is recognized as being complementary to a very specific mRNA sequence. (genomicglossaries.com)
  • Pharmaceutical biology antisense, antisense DNA, antisense oligonucleotides. (genomicglossaries.com)
  • Therapeutic oligonucleotides, such as antisense oligonucleotides or ribozymes, are short segments of DNA that have been designed to hybridize to a sequence on a specific mRNA. (justia.com)
  • 1993. Inhibition of HIV-1 Replication in Cultured Cells with Antisense Oligonucleotides Encapsulated in Immunoliposomes. (justia.com)
  • Here, we report that the miRNA iab-4 locus in the Drosophila Hox cluster is transcribed convergently from both DNA strands, giving rise to two distinct functional miRNAs. (nih.gov)
  • Exact mass measurements for the sense and antisense strands of the dsDNA amplicon reported. (cdc.gov)
  • Antisense molecules are strands of RNA that are designed to link onto complementary targeted strands of messenger RNA. (sciencedaily.com)
  • They form more stable hybrids with complementary RNA strands than equivalent DNA/RNA sequences. (eurogentec.com)
  • The most frequent site of alkylation in DNA is the O 6 position of guanine, which forms cross-links between adjacent strands of DNA, leading to cell death. (aacrjournals.org)
  • Conserved expression of natural antisense transcripts in mammals. (sdstate.edu)
  • A sensitive and specific fluorescence in situ hybridisation protocol was combined with protein immunostaining to show that both sense and antisense foci were frequent, specific to C9FTLD, and present in neurons of the frontal cortex, hippocampus and cerebellum. (nih.gov)
  • In the present study, we designed an antisense oligodeoxynucleotide of DNMT1 (AS/MT: 5′-CGGTAC GCGCCGGCATCT-3′) and demonstrated successful inhibition of DNMT1 expression by AS/MT at the protein level, using gastric cancer cell lines in vitro. (elsevierpure.com)
  • Here we show that high-mobility group AT-hook 2 protein (HMGA2) induces DNA nicks at the transcription start site, which are required by the histone chaperone FACT complex to incorporate nucleosomes containing the histone variant H2A.X. Further, phosphorylation of H2A.X at S139 (γ-H2AX) is required for repair-mediated DNA demethylation and transcription activation. (nature.com)
  • Active DNA demethylation also requires GADD45A (growth arrest and DNA damage protein 45 alpha) and TET1 (ten-eleven translocation methylcytosine dioxygenase 1), which sequentially oxidize 5-methylcytosine (5mC) to 5-carboxylcytosine (5caC) 18 , 19 and are cleared through DNA repair mechanisms. (nature.com)
  • In a cell, antisense DNA serves as the template for producing messenger RNA (mRNA), which directs the synthesis of a protein. (genome.gov)
  • Dharmacon Reagents support researchers on this journey at the DNA, RNA, and protein level with the broadest range of functional genomic tools including industry leading gene modulation and gene editing solutions to help elucidate complex biological networks for functional genomic studies. (horizondiscovery.com)
  • Highly specific and effective gene silencing of any disease can be achieved by an accurate knowledge of the target mRNA sequence and rational design of its complementary antisense agents for the downregulation of its protein message. (genomicglossaries.com)
  • The DNA repair protein O 6 -methylguanine-DNA methyltransferase (MGMT) plays an important role in cellular resistance to alkylating agents. (aacrjournals.org)
  • A cellular DNA-repair protein, namely O 6 -methylguanine-DNA methyltransferase (MGMT) protein, reverses alkylation at the O 6 position of guanine, thereby inhibiting the lethal cross-linking and bringing about resistance to alkylating agents ( 2, 3 ). (aacrjournals.org)
  • Genes and Chromosomes Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body or the code for functional ribonucleic. (msdmanuals.com)
  • Cotransfection of the cells with a mixture of plasmid DNA consisting of TIF3 cDNA in the sense and in the antisense orientation resulted in significant inhibition of translation of the TIF3 protein. (cdc.gov)
  • Antisense (3'-->5') TIF3 mRNA-mediated inhibition of translation of TIF3 protein, furthermore, resulted in inhibition of TIF3-mediated transformation of NIH3T3 cells as evidenced from the decrease in the number of transformed foci. (cdc.gov)
  • Five plasmid protein antitoxin-regulated systems and three plasmid antisense RNA-regulated systems were sought by PCR. (who.int)
  • RNA molecules which hybridize to complementary sequences in either RNA or DNA altering the function of the latter. (genomicglossaries.com)
  • Using antisense technology, modified RNA molecules can combine with specific parts of the DNA, preventing the affected genes from functioning. (msdmanuals.com)
  • Rapid identification of intact bacterial resistance plasmids via optical mapping of single DNA molecules. (cdc.gov)
  • DNA (cytosine-5-)-methyltransferase 1 (DNMT1) plays an important role in the maintenance of DNA methylation patterns via complicated networks including signaling pathways and transcriptional factors, relating to cell differentiation or carcinogenesis. (elsevierpure.com)
  • In conclusion, the inhibition of DNA methylation by DNMT1 by an antisense oligodeoxynucleotide influences cell morphology and adhesion, as well as cell growth in gastric cancer cells in vitro. (elsevierpure.com)
  • Moreover, these alterations in the characteristics of cancer cells resulted in an increased ability to attach onto the peritoneum in the nude mouse system in vivo, suggesting that strict clinical guidelines will be necessary to utilize such a DNA methylation inhibitor, since it does not always mean a therapeutic antitumor strategy. (elsevierpure.com)
  • Chromatin-mediated regulation of transcription involves DNA methylation and histone modifications. (nature.com)
  • Here we report genome-wide composition, patterning, and stage-specific dynamics of DNA methylation in pre-implantation rhesus monkey embryos as well as male and female gametes studied using an optimized tagmentation-based whole-genome bisulfite sequencing method. (nature.com)
  • We show that upon fertilization, both paternal and maternal genomes undergo active DNA demethylation, and genome-wide de novo DNA methylation is also initiated in the same period. (nature.com)
  • By the 8-cell stage, remethylation becomes more pronounced than demethylation, resulting in an increase in global DNA methylation. (nature.com)
  • Our study provides the first comprehensive illustration of the 'wax and wane' phases of DNA methylation dynamics. (nature.com)
  • Most importantly, our DNA methyltransferase loss-of-function analysis indicates that DNA methylation influences early monkey embryogenesis. (nature.com)
  • DNA CpG methylation on the cytosine is among the most stable forms of epigenetic mechanisms in the life cycle of mammals. (nature.com)
  • We therefore decided to investigate comprehensively the global and high-resolution DNA methylation dynamics during early development of a non-human primate (rhesus monkey, Macaca mulatta ). (nature.com)
  • Monkeys have served as one of the most valuable models for understanding DNA methylation dynamics during early embryogenesis in human due to their similarities in genetics and early embryonic development 17 , 18 . (nature.com)
  • We performed a systematic analysis of blood DNA methylation profiles from 4,483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia and treatment-resistant schizophrenia. (elifesciences.org)
  • Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. (elifesciences.org)
  • Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. (elifesciences.org)
  • Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia. (elifesciences.org)
  • We also show that SpCas9-mediated cleavage is unaffected by DNA methylation and that the dosage of SpCas9 and sgRNA can be titrated to minimize off-target modification. (cdc.gov)
  • Several techniques, called RNA therapies, use pieces of RNA, which is a type of genetic material similar to DNA, to help treat a disorder. (medlineplus.gov)
  • Both sense and antisense miRNA products target neighboring Hox genes via highly conserved sites, leading to homeotic transformations when ectopically expressed. (nih.gov)
  • January 21, 2021 -- Using an engineered DNA therapeutic agent to silence transcription factor genes reduced myeloma stem cell abundance and increased the survival of mice bearing human myeloma, according to preclinical study data published in Cell Stem Cell on January 20. (scienceboard.net)
  • Synthetic antisense RNAs are used to effect the functioning of specific genes for investigative or therapeutic purposes. (genomicglossaries.com)
  • Epigenetic changes are specific modifications (often called "tags") attached to DNA that control whether genes are turned on or off. (medlineplus.gov)
  • In antisense technology, normal genes are not inserted. (msdmanuals.com)
  • Los ARNs antisentido sintéticos se utilizan para afectar el funcionamiento de genes específicos en la investigación o con fines terapéuticos. (bvsalud.org)
  • One technique that is garnering wide attention in this realm is the DNA array, in which a number of different genes from an individual can be processed to look at certain genotypes. (medscape.com)
  • For example, in the hereditary cancer syndromes familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, mutations have been discovered in the APC gene and DNA mismatch repair genes. (medscape.com)
  • Antisense technology uses knowledge of the genetic code by which DNA passes along instructions to messenger RNA, which in turn produces proteins that perform biological functions. (sciencedaily.com)
  • These drugs work by suppressing and destroying the viral messenger RNA, which is crucial to make proteins and replicate HBV DNA. (hepb.org)
  • Clinical trials have shown effective reduction in HBV DNA and viral proteins. (hepb.org)
  • UC San Diego School of Medicine and Ionis Pharmaceuticals have a long history of collaborating on the development of investigational antisense medicines. (scienceblog.com)
  • We also report sense/antisense miRNAs in mouse and find antisense transcripts close to many miRNAs in both flies and mammals, suggesting that additional sense/antisense pairs exist. (nih.gov)
  • These results further confirm that overexpression of TIF3 is oncogenic and the antisense TIF3 mRNA expression reverses its oncogenic potential. (cdc.gov)
  • Antisense inhibition of translation initiation factor 3 reverses its oncogenic potential. (cdc.gov)
  • Interestingly, TGFB signaling has been reported to induce active DNA demethylation with the involvement of thymidine DNA glycosylase (TDG) 17 . (nature.com)
  • Complete Cure: Elimination of all traces of hepatitis B including loss of surface antigen and HBV DNA. (hepb.org)
  • Functional Cure: the loss of hepatitis B surface antigen and undetectable HBV DNA levels, although trace amounts of HBV DNA may persist in the liver. (hepb.org)
  • PNA provides a powerful tool to study the mechanism of transcription and an innovative strategy to regulate target gene expression, antisense, antigen agents, molecular probes, and biosensors. (pr.com)
  • An allele is one of two or more versions of DNA sequence (a single base or a segment of bases) at a given genomic location. (genome.gov)
  • Analysis of genomic DNA shows a simple pattern for Sgt2 indicative of low copy number. (usda.gov)
  • Dr Kasuya Motomura amplification bias, we assessed genome secondary events reflecting progressive wide chromosomal imbalance by array genomic instability, a hallmark of CGH (Agilant 105K) in DNA from 2-5 glioblastomas. (who.int)
  • The DNA sequence and comparative analysis of human chromosome 10. (nih.gov)
  • A codon is a DNA or RNA sequence of three nucleotides (a trinucleotide) that forms a unit of genetic information encoding a particular amino acid. (genome.gov)
  • Experimentally observed masses were within ±1ppm of expected masses, based on sequence data for each of the amplified DNA. (cdc.gov)
  • Dust off that old Simon(TM) game and give it a new lease on life -- as a sleekly functional DNA sequence entry device! (halfbakery.com)
  • What a great format for DNA sequence entry! (halfbakery.com)
  • We find that SpCas9 tolerates mismatches between guide RNA and target DNA at different positions in a sequence-dependent manner, sensitive to the number, position and distribution of mismatches. (cdc.gov)
  • PNAs are synthetic DNA, or RNA, mimics that consist of nucleobases attached to a polyamide backbone. (pr.com)
  • Although the genome-wide DNA demethylation is believed to be a hallmark of mammalian embryogenesis, previous study also indicated that the somatic form of dnmt1 ( dnmt1s ) is actually expressed at each stage of pre-implantation embryos and plays a role in the maintenance of DNA imprinting 8 . (nature.com)
  • 90%) low-grade diffuse gliomas DNA demethylation. (who.int)
  • However, none of these solutions have proven entirely satisfactory, and in vivo free antisense still has only limited efficacy. (justia.com)
  • However, robust and large-scale genome-wide reprogramming of DNA methylome occurs during two critical developmental processes: (1) development of primordial germ cells and (2) pre-implantation embryogenesis. (nature.com)
  • presents an opportunity to manipulate gene expression within the cells to treat various diseases, and acts as a powerful tool for studying gene function utilizing antisense agents to manage the diseases by regulating the expression of the specific factor that actually causes the particular disease. (genomicglossaries.com)
  • Many phage have proved useful in the study of molecular biology and as vectors for the transfer of genetic information between cells lambda bacteriophage can also undergo a lytic cycle or can enter a lysogenic cycle, in which the page DNA is incorporated into that of the host, awaiting a signal that initiates events leading to replication of the virus and lysis of the host cell. (genomicglossaries.com)
  • The transfer of the normal DNA into a person's cells can be done by several methods. (msdmanuals.com)
  • The normal DNA is inserted by a chemical reaction into the virus, which then infects (transfects) the person's cells, thereby transmitting the DNA into the nucleus of those cells. (msdmanuals.com)
  • Another concern is that the new, normal DNA may become "lost" or may fail to be incorporated into new cells after some period of time, leading to the reappearance of the genetic disorder. (msdmanuals.com)
  • Liposomes can be configured to contain DNA that can be absorbed by the person's cells, thereby delivering their DNA to the cell nucleus. (msdmanuals.com)
  • Using the SURVEYOR nuclease assay 13 , we assessed the ability of each Cas9-sgRNA complex to generate indels in human embryonic kidney (HEK) 293FT cells through the induction of DNA doublestranded breaks (DSBs) and subsequent nonhomologous end joining (NHEJ) DNA damage repair (Online Methods). (cdc.gov)
  • Publications] Noriaki Sugawa, Satoshi Ueda: 'Gene therapy using antisense DNA' Clinical Neuroscience. (nii.ac.jp)
  • Advanced human clinical assessments of several antisense drugs are currently underway. (justia.com)
  • Microorganism detection methods that detect microbial DNA rather than the microorganisms themselves have been introduced in both research and clinical laboratories. (bvsalud.org)
  • commonly known as γ-H2AX, further referred to as pH2A.X) is used as a marker for DNA double-strand breaks 6 . (nature.com)
  • Adenine (A) is one of the four nucleotide bases in DNA, with the other three being cytosine (C), guanine (G) and thymine (T). Within a double-stranded DNA molecule, adenine bases on one strand pair with thymine bases on the opposite strand. (genome.gov)
  • Antisense is the non-coding DNA strand of a gene. (genome.gov)
  • Sense and antisense strand base compositions reported. (cdc.gov)
  • aRNA is RNA that is transcribed from the coding, rather than the template, strand of DNA. (genomicglossaries.com)
  • 1997. Antisense: Chemical Modifications. (justia.com)
  • Scientists are creating unthinkable genetic modifications in our food, mixing animal, insects and even human DNA into animals and plants, and the reason of course is the giant biotechnology corporations are desperate for profits at any cost. (jesus-is-savior.com)
  • sgRNAs with +67 or +85 nucleotide (nt) tracrRNA tails mediated DNA cleavage at all target sites tested, with up to fivefold higher levels of indels than the corresponding crRNA-tracrRNA duplexes ( Fig. 1b and Supplementary Fig. 1a ). (cdc.gov)
  • An amino terminal fragment of Sgt2 was used to create an antisense transgene under control the Gbss6 promoter and the Ubi3 polyadenylation signal. (usda.gov)
  • Viral cell-free DNA (cfDNA) in plasma has been widely evaluated for detecting cancer and monitoring disease in virus-associated tumors. (bvsalud.org)
  • pp147-161 in Gene Regulation: Biology of Antisense RNA and DNA (Eds. (justia.com)
  • Conversely, suppressing PA degradation by inhibiting LPP activity using any of three different inhibitors significantly stimulated pollen tube growth, and similar effect was achieved by suppressing the expression of tobacco pollen LPP4 using antisense knock-down. (frontiersin.org)
  • Antisense can also effect cellular activity by hybridizing specifically with chromosomal DNA. (justia.com)
  • Problems remain, such as in the limited ability of some antisense to cross cellular membranes (see, Vlassov, et al. (justia.com)
  • Our data support the concept that chromatin opening during transcriptional initiation involves intermediates with DNA breaks that subsequently require DNA repair mechanisms to ensure genome integrity. (nature.com)
  • One method is to use a virus because certain viruses have the ability to insert their genetic material into human DNA. (msdmanuals.com)
  • As of 2003, 99% of the chemical base pairs that make up human DNA had been sequenced to within 99.99% accuracy. (medscape.com)
  • We present the first definitive report of C9orf72 repeat sense and antisense RNA foci using a series of C9FTLD cases, and neurodegenerative disease and normal controls. (nih.gov)
  • These data establish that sense and antisense C9orf72 repeat RNA foci are a consistent and specific feature of C9FTLD, providing new insight into the pathogenesis of C9FTLD. (nih.gov)
  • It is activated by DNA that contains motifs, which are frequently present in bacterial DNA. (izb-online.de)
  • A different method of gene therapy uses antisense technology. (msdmanuals.com)
  • EFMC-ISMC 2022 will also feature most recent advances in new technologies such as the exploitation of RNA as drug target, artificial intelligence in drug discovery, natural products-based drug discovery, DNA encoded libraries applications and the development of covalent drugs, PROTACs and molecular glues. (efmc.info)
  • The discovery of the structure of DNA by Francis Crick and James Watson in the early 1950s ushered in a new era in molecular biologic science. (medscape.com)
  • In the eukaryotic cell nucleus, chromatin is the physiological template of all DNA-dependent processes including transcription. (nature.com)
  • The antitat research combines gene therapy with another promising approach in genetically based medicine: antisense therapy. (sciencedaily.com)
  • Nous avons examiné 132 agents de santé à la recherche d'ADN du virus de l'hépatite B (VHB) au moyen de l'amplification en chaîne par polymérase (PCR) nichée et de l'anticorps du virus de l'hépatite C (anti-VHC) par la méthode ELISA. (who.int)
  • En conclusion, les agents de santé égyptiens ont un taux d'hépatite B occulte significatif et le génotype E du VHB est prévalent. (who.int)