Drug Delivery Systems and Liver Targeting for the Improved Pharmacotherapy of the Hepatitis B Virus (HBV) Infection

Cuestas, María Luján; Mathet, Verónica Lidia; Oubiña, José R.; Sosnik, Alejandro

doi:10.1007/s11095-010-0112-z

Cited by 26 publications

(23 citation statements)

References 121 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fortunately, the liver appears to be an organ favoring the induction of immune tolerance (42) and is accessible to a number of nucleic acid delivery methods (43,44). Therefore, any novel anti-HBV therapy has an inherent advantage.…”

Section: Discussionmentioning

confidence: 99%

An Efficient Antiviral Strategy for Targeting Hepatitis B Virus Genome Using Transcription Activator-Like Effector Nucleases

et al. 2014

View full text Add to dashboard Cite

The hepatitis B virus (HBV) is a DNA virus that can cause chronic hepatitis B (CHB) in humans. Current therapies for CHB infection are limited in efficacy and do not target the pre-existing viral genomic DNA, which are present in the nucleus as a covalently closed circular DNA (cccDNA) form. The transcription activator-like (TAL) effector nucleases (TALENs) are newly developed enzymes that can cleave sequence-specific DNA targets. Here, TALENs targeting the conserved regions of the viral genomic DNA among different HBV genotypes were constructed. The expression of TALENs in Huh7 cells transfected with monomeric linear full-length HBV DNA significantly reduced the viral production of HBeAg, HBsAg, HBcAg, and pgRNA, resulted in a decreased cccDNA level and misrepaired cccDNAs without apparent cytotoxic effects. The anti-HBV effect of TALENs was further demonstrated in a hydrodynamic injection-based mouse model. In addition, an enhanced antiviral effect with combinations of TALENs and interferon-α (IFN-α) treatment was observed and expression of TALENs restored HBV suppressed IFN-stimulated response element-directed transcription. Taken together, these data indicate that TALENs can specifically target and successfully inactivate the HBV genome and are potently synergistic with IFN-α, thus providing a potential therapeutic strategy for treating CHB infection.

show abstract

Section: Discussionmentioning

confidence: 99%

An Efficient Antiviral Strategy for Targeting Hepatitis B Virus Genome Using Transcription Activator-Like Effector Nucleases

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The S-ORF includes the sequence assumed to codify the binding sites for the hepatocyte and has three in-frame AUG codons dividing this ORF into three regions, known as Pre-S1, Pre-S2, and S, encoding for these homonym viral envelope proteins [13]. The C-ORF has two initiation codons encoding for the structural protein of the nucleocapsid, which plays an important role in viral particle assembly (hepatitis B core antigen [HBcAg]), and a soluble antigen secreted by infected cells (hepatitis B e antigen [HBeAg]) [14]. The X-ORF encodes for the hepatitis B x antigen [HBxAg], which displays trans-activating activity and other regulatory functions [15].…”

Section: The Structure Of Hepatitis B Virusmentioning

confidence: 99%

“…The X-ORF encodes for the hepatitis B x antigen [HBxAg], which displays trans-activating activity and other regulatory functions [15]. Finally, the P-ORF encodes for a multifunctional enzyme, the polymerase, which constitutes the current target for the nucleos(t)ide analogues used in the treatment of CHB [14].…”

Section: The Structure Of Hepatitis B Virusmentioning

confidence: 99%

Hepatitis B Virus (HBV) and S-Escape Mutants: From the Beginning until Now

Maria¹

2015

JHVRV

View full text Add to dashboard Cite

Despite of the progress made in vaccine and antiviral therapy development, hepatitis B virus (HBV) infection remains a major health care problem. More than 240 million people are chronically infected worldwide showing differences in the severity of liver disease, clinical outcome and response to immune-and antiviraltherapy. Parameters associated with the host immune system (HBV specific Tand/or B-cell repertoires, defective antigen presentation and diminished Th1/ Th2 response ratio) and viral factors such as the HBV genotypes and their evolving variants/mutants, have largely contributed to explaining such differences. The unique genomic structure and replication cycle of HBV provide much opportunity for mutations to occur in any of its genes undergoing selection pressures, such as those associated with the host immune system, the hepatitis B vaccine and/ or hepatitis B immune globulin and the antiviral therapy with nucleos(t)ide analogues. Firstly, this review describes the current prevalence of S-escape mutants worldwide. Secondly, the clinical implications of such surface gene variants and the impact of universal hepatitis B vaccination on HBV mutations and genotypes are discussed. Finally, the fact that the immune escape process also extends well beyond HBV is addressed.

show abstract

“…[86,87] The pathogenesis and clinical outcomes of HBV infection depend on viral factors, such as lifecycle and genotypic variants, and host immune response (i.e. viral persistence).…”

Section: Hepatitis B Virusmentioning

confidence: 99%

Medical Management of Chronic Liver Diseases in Children (Part I)

El-Shabrawi

Kamal

2011

Pediatric Drugs

View full text Add to dashboard Cite

The management of children with chronic liver disease (CLD) mandates a multidisciplinary approach. CLDs can be classified into 'potentially' curable, treatable non-curable, and end-stage diseases. Goals pertaining to the management of CLDs can be divided into prevention or minimization of progressive liver damage in curable CLD by treating the primary cause; prevention or control of complications in treatable CLD; and prediction of the outcome in end-stage CLD in order to deliver definitive therapy by surgical procedures, including liver transplantation. Curative, specific therapies aimed at the primary causes of CLDs are, if possible, best considered by a pediatric hepatologist. Medical management of CLDs in children will be reviewed in two parts, with part I (this article) specifically focusing on 'potentially' curable CLDs. Dietary modification is the cornerstone of management for galactosemia, hereditary fructose intolerance, and certain glycogen storage diseases, as well as non-alcoholic steatohepatitis. It is also essential in tyrosinemia, in addition to nitisinone [2-(nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione] therapy, as well as in Wilson disease along with copper-chelating agents such as D-penicillamine, triethylenetetramine dihydrochloride, and ammonium tetrathiomolybdate. Zinc and antioxidants are adjuvant drugs in Wilson disease. New advances in chronic viral hepatitis have been made with the advent of oral antivirals. In children, currently available drugs for the treatment of chronic hepatitis B virus infection are standard interferon (IFN)-α-2, pegylated IFN-α-2 (PG-IFN), and lamivudine. In adults, adefovir and entecavir have also been licensed, whereas telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine, and thymosin α-1 are currently undergoing clinical testing. For chronic hepatitis C virus infection, the most accepted treatment is PG-IFN plus ribavirin. Corticosteroids, with or without azathioprine, remain the basic strategy for inducing remission in autoimmune hepatitis. Ciclosporin (cyclosporine) and other immune suppressants may be used for patients who do not achieve remission, or who have significant side effects, with corticosteroid/azathioprine therapy. The above therapies can prevent, or at least minimize, progression of liver damage, particularly if started early, leading to an almost normal quality of life in affected children.

show abstract

Drug Delivery Systems and Liver Targeting for the Improved Pharmacotherapy of the Hepatitis B Virus (HBV) Infection

Cited by 26 publications

References 121 publications

An Efficient Antiviral Strategy for Targeting Hepatitis B Virus Genome Using Transcription Activator-Like Effector Nucleases

An Efficient Antiviral Strategy for Targeting Hepatitis B Virus Genome Using Transcription Activator-Like Effector Nucleases

Hepatitis B Virus (HBV) and S-Escape Mutants: From the Beginning until Now

Medical Management of Chronic Liver Diseases in Children (Part I)

Contact Info

Product

Resources

About