A perspective on RNA interference-based therapeutics for metabolic liver diseases.

Abstract:

:Introduction: Therapeutic oligonucleotides have emerged as a promising new class of drug that could silence undruggable targets; they can potentially treat metabolic liver diseases such as nonalcoholic fatty liver disease (NAFLD), hereditary hemochromatosis and alpha 1 antitrypsin deficiency. Areas covered: This article illuminates the mechanism of action of, and drug delivery approaches for therapeutic oligonucleotides such as antisense oligonucleotides (ASOs), short interfering RNAs (siRNAs), and MicroRNAs (miRs). We reveal why the liver is the ideal organ for therapeutic oligonucleotides, discuss its unique architecture, and shed light on those susceptible molecular targets that can be modulated. We also examine preclinical and clinical data on the utility of oligonucleotides in silencing the expression of genes responsible for metabolic liver diseases. Expert opinion: The liver has numerous susceptible molecular therapeutic targets; hence, metabolic liver diseases can be treated effectively by modulating these targets via novel therapeutic oligonucleotides. Undoubtedly, these exciting developments integrate well with precision medicine progress. Specific therapeutic oligonucleotides can be designed based on the exact underlying molecular mechanism of the disease. So, there is a justification for furthering the development of therapeutic oligonucleotides for metabolic liver diseases. Safety concerns such as immunogenicity and off-target effects will however require careful monitoring.

authors

Alkhouri N,Gawrieh S

doi

10.1080/13543784.2021.1879792

subject

Has Abstract

pub_date

2021-01-29 00:00:00

pages

1-7

eissn

1354-3784

issn

1744-7658

pub_type

杂志文章
  • Fospropofol disodium, a water-soluble prodrug of the intravenous anesthetic propofol (2,6-diisopropylphenol).

    abstract:BACKGROUND:Today, propofol or 2,6-diisopropylphenol is the anesthetic mainly used for monitored anesthetic care sedation and during intravenous anesthesia. The formulation, a lipid macroemulsion, shows several disadvantages. Therefore, during the past years considerable scientific effort has been undertaken to find eit...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543780903193063

    authors: Fechner J,Ihmsen H,Jeleazcov C,Schüttler J

    更新日期:2009-10-01 00:00:00

  • Novel therapeutic strategies targeting vascular endothelium in essential hypertension.

    abstract:IMPORTANCE OF THE FIELD:Several studies have demonstrated the high prevalence of hypertension and the crucial role of the association between endothelial function and hypertension. Thus, in depth investigation of the pathophysiological mechanisms linking endothelial dysfunction and hypertension, as well as evaluation o...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2010.522989

    authors: Tousoulis D,Papageorgiou N,Androulakis E,Paroutoglou K,Stefanadis C

    更新日期:2010-11-01 00:00:00

  • Investigational Janus kinase inhibitors in development for myelofibrosis.

    abstract:INTRODUCTION:Since the discovery of the activating V617F mutation in Janus kinase 2 (JAK2), a number of pharmacologic inhibitors of JAK2 have entered clinical trials for patients with myelofibrosis. However, ruxolitinib, approved in 2011, remains the only one currently available for treatment of myelofibrosis, with man...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2017.1323871

    authors: Bose P,Abou Zahr A,Verstovsek S

    更新日期:2017-06-01 00:00:00

  • The therapeutic potential of testosterone patches.

    abstract::In the last decade, transdermal delivery of testosterone (T) has been shown to be a safe and effective means of treating male hypogonadism. Transdermal T patches can provide for physiologic androgen replacement in over 90% of men with hypogonadism. In addition, T patches have been shown to be equivalent to im. T ester...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.7.12.1977

    authors: Amory JK,Matsumoto AM

    更新日期:1998-12-01 00:00:00

  • Toll-like receptor modulation in cardiovascular disease: a target for intervention?

    abstract::Toll-like receptors (TLRs) form a family of pattern recognition receptors that have emerged as key mediators of innate immunity. These receptors sense invading microbes and initiate the immune response. TLR-mediated inflammation is an important pathogenic link between innate immunity and a diverse panel of clinical di...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.15.8.857

    authors: Földes G,von Haehling S,Anker SD

    更新日期:2006-08-01 00:00:00

  • Triple-drug chemotherapy regimens in combination with an anti-EGFR agent in metastatic colorectal cancer - prospects from phase II clinical trials.

    abstract:INTRODUCTION:The addition of monoclonal antibody (mAb) epidermal growth factor receptor (EGFR) inhibitors to classic chemotherapy doublet backbones has improved survival of metastatic colorectal cancer (mCRC). However, the role of triple-drug chemotherapy regimens in combination with an anti-EGFR mAb inhibitor is not y...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2019.1599860

    authors: Matos I,Noguerido A,Ros J,Mulet N,Argilés G,Elez É,Tabernero J

    更新日期:2019-05-01 00:00:00

  • Targeting tyrosine-kinases in ovarian cancer.

    abstract:INTRODUCTION:Epithelial ovarian cancer (EOC) is the leading cause of gynaecologic cancer death. Although in some cases initial treatment is effective, most of the women diagnosed with EOC will probably need medical treatment for their disease. There is a critical need to develop effective new strategies for the managem...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2013.816282

    authors: Morotti M,Becker CM,Menada MV,Ferrero S

    更新日期:2013-10-01 00:00:00

  • Angiotensin II type 2 receptor agonists--where should they be applied?

    abstract::It is now widely accepted that the renin-angiotensin system (RAS) not only contributes to pathological mechanisms involved, e.g. in hypertension or hypertensive and diabetic end-organ damage, but also harbors a "protective arm" represented mainly by two receptors, the AT2 (angiotensin type 2) receptor and the Mas rece...

    journal_title:Expert opinion on investigational drugs

    pub_type: 评论,杂志文章

    doi:10.1517/13543784.2012.681046

    authors: Steckelings UM,Unger T

    更新日期:2012-06-01 00:00:00

  • The therapeutic potential of gut hormone peptide YY3-36 in the treatment of obesity.

    abstract::Many peptides are synthesised and released from the gastrointestinal tract. Although their roles in the regulation of gastrointestinal function have been known for some time, it has become increasingly evident that they also influence eating behaviour. Peptide YY (PYY) is released postprandially from gastrointestinal ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.14.5.647

    authors: Small CJ,Bloom SR

    更新日期:2005-05-01 00:00:00

  • Second-generation epidermal growth factor tyrosine kinase inhibitors in non-small cell lung cancer.

    abstract::Inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) has an established role in the treatment of advanced non-small cell lung cancer. The first-generation EGFR inhibitors erlotinib and gefitinib have been approved for treatment in the second- and third-line setting. Second-generation ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543780902762843

    authors: Mukherji D,Spicer J

    更新日期:2009-03-01 00:00:00

  • Sofinicline: a novel nicotinic acetylcholine receptor agonist in the treatment of attention-deficit/hyperactivity disorder.

    abstract:INTRODUCTION:Psychostimulants are first-line treatments for attention-deficit/hyperactivity disorder (ADHD), but their tolerability profiles and individual response variability fuel a continuing search for alternative medications. The observation that nicotinic agents improve cognition has led pharmaceutical companies ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2014.934806

    authors: Fleisher C,McGough J

    更新日期:2014-08-01 00:00:00

  • AIT-082, a novel purine derivative with neuroregenerative properties.

    abstract::Preclinical and clinical evidence support the effectiveness of neurotrophins in Alzheimer's disease (AD) and neurodegenerative diseases. Delivery of neurotrophins to target sites in the brain remains a major obstacle for their use in humans. Development of orally active agents that mimic the effects of nerve growth fa...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.6.10.1413

    authors: Glasky AJ,Glasky MS,Ritzmann RF,Rathbone MP

    更新日期:1997-10-01 00:00:00

  • Aripiprazole: a partial dopamine D2 receptor agonist antipsychotic.

    abstract::This paper reviews the clinical pharmacology, efficacy and safety of the novel antipsychotic drug aripiprazole. All published citations regarding aripiprazole were reviewed using a Medline((R)) search (completed for citations through mid-year, 2002). In addition, abstracts from recent scientific meetings presenting da...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.12.4.655

    authors: Keck PE Jr,McElroy SL

    更新日期:2003-04-01 00:00:00

  • Insulin sensitizers in 2013: new insights for the development of novel therapeutic agents to treat metabolic diseases.

    abstract::Insulin-sensitizing thiazolidinediones (TZDs) correct a root cause of type 2 diabetes and potentially other diseases of metabolic dysfunction, including conditions ranging from oncologic, inflammatory, and neurodegenerative diseases. Importantly, compounds with this mode of action can modify disease progression, as op...

    journal_title:Expert opinion on investigational drugs

    pub_type: 社论,评审

    doi:10.1517/13543784.2013.839659

    authors: Colca JR,Tanis SP,McDonald WG,Kletzien RF

    更新日期:2014-01-01 00:00:00

  • Proteasome inhibition for the treatment of glioblastoma.

    abstract:INTRODUCTION:Glioblastoma is a primary brain tumor with a poor prognosis despite multimodal therapy including surgery, radiotherapy and alkylating chemotherapy. Novel therapeutic options are therefore urgently needed; however, there have been various drug failures in late-stage clinical development. The proteasome repr...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1080/13543784.2020.1803827

    authors: Roth P,Mason WP,Richardson PG,Weller M

    更新日期:2020-10-01 00:00:00

  • Pompholyx: what's new?

    abstract:BACKGROUND:Pompholyx is a chronic relapsing inflammatory vesicobullous skin disease of the hands and feet belonging to the spectrum of eczema. Established treatments, both topical and systemic, are limited in efficacy, risk:benefit ratio and prevention of further relapses. New treatment options are needed. OBJECTIVE:T...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.17.6.897

    authors: Wollina U

    更新日期:2008-06-01 00:00:00

  • Histone deacetylase inhibitors in clinical development.

    abstract::In addition to a variety of other novel agents, interest in histone deacetylase inhibitors (HDACIs) as antineoplastic drugs has recently accelerated and increasing numbers of these compounds have entered clinical trials in humans. HDACIs represent a prototype of molecularly targeted agents that perturb signal transduc...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.13.1.21

    authors: Rosato RR,Grant S

    更新日期:2004-01-01 00:00:00

  • Contraceptives with novel benefits.

    abstract:INTRODUCTION:Progesterone receptor (PR) agonists (progestins) and antagonists are developed for female contraceptives. However, non-contraceptive applications of newer progestins and PR modulators are being given more attention. AREAS COVERED:The newer PR agonists including drospirenone, nomegestrol, trimegestone, die...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2012.642368

    authors: Su Y,Lian QQ,Ge RS

    更新日期:2012-01-01 00:00:00

  • Combination therapy with the type II anti-CD20 antibody obinutuzumab.

    abstract:INTRODUCTION:Obinutuzumab is a novel humanized type II glycoengineered anti-CD20 antibody approved for first-line treatment of chronic lymphocytic leukemia (CLL) in combination with chlorambucil and for treatment of rituximab-refractory follicular lymphoma (FL). Areas covered: We describe current preclinical and clinic...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2017.1373087

    authors: Klein C,Bacac M,Umana P,Fingerle-Rowson G

    更新日期:2017-10-01 00:00:00

  • Telomerase inhibitors for the treatment of cancer: the current perspective.

    abstract::Telomerase is a holoenzyme responsible for the maintenance of telomeres, the protein-nucleic acid complexes at the ends of eukaryotic chromosomes that serve to maintain chromosomal stability and integrity. Telomerase activity is essential for the sustained proliferation of most immortal cells, including cancer cells. ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.10.12.2141

    authors: Perry PJ,Arnold JR,Jenkins TC

    更新日期:2001-12-01 00:00:00

  • Ixabepilone for the treatment of solid tumors: a review of clinical data.

    abstract:BACKGROUND:Microtubule stabilizing agents such as taxanes are an integral part of therapy for multiple solid tumors. However, due to limitations of these agents, newer more effective cytotoxic agents are necessary. Ixabepilone, an epothilone B analog, is a novel microtubule stabilizing agent. OBJECTIVE:This review pro...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.17.3.423

    authors: Denduluri N,Swain SM

    更新日期:2008-03-01 00:00:00

  • Current status and future development of antitubercular chemotherapy.

    abstract::Tuberculosis (TB), which kills more people than any other infectious disease, was declared a global emergency by the World Health Organization in 1993. The emergence of new Mycobacterium tuberculosis strains that are resistant to some or all current antitubercular drugs seriously hampers the control of the disease. Up...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.11.8.1033

    authors: Kremer LS,Besra GS

    更新日期:2002-08-01 00:00:00

  • Treatment of hyperlipidaemia with fenofibrate and related fibrates.

    abstract:BACKGROUND:Fenofibrate is the most widely used fibrate. Its efficacy and tolerability in the treatment of hypertriglyceridaemia and combined hyperlipidaemia have been demonstrated in several clinical trials. OBJECTIVE:To review the pharmacology, lipid-lowering and extra-lipid effects of fenofibrate and to preview ABT-...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.17.10.1599

    authors: Filippatos T,Milionis HJ

    更新日期:2008-10-01 00:00:00

  • The development of antibody delivery systems to target cancer with highly potent maytansinoids.

    abstract::Improving the tumour selectivity of cytotoxic drugs through conjugation to tumour-reactive monoclonal antibodies may lead to novel, more potent agents for cancer therapy. The maytansinoid drugs are 100- to 1000-fold more cytotoxic in vitro than current clinical anticancer drugs. We recently demonstrated that conjugati...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.6.2.169

    authors: Liu C,Chari RV

    更新日期:1997-02-01 00:00:00

  • Pharmacological revascularisation in coronary and peripheral vascular disease.

    abstract::Therapeutic angiogenesis is a novel approach to the treatment of ischaemic or occlusive coronary and peripheral vascular disease. The therapeutic concept is based on the restoration of distal blood flow by the enlargement of existing vessels and tissue perfusion by the induction of new capillaries. Initial studies hav...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.13.10.1319

    authors: Tarzami ST,Singh JP

    更新日期:2004-10-01 00:00:00

  • Is everolimus useful in preventing allograft rejection and vasculopathy after heart transplant?

    abstract::The main cause of illness and death after the first year of heart transplantation is vasculopathy of the cardiac allograft, probably initiated by early immunological and non-immunological endothelial damage. The incidence of multiple episodes of grade 3A rejection 6 months after primary heart transplantation was lower...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.13.2.161

    authors: Doggrell SA

    更新日期:2004-02-01 00:00:00

  • Investigational therapies targeting the androgen signaling axis and the androgen receptor and in prostate cancer - recent developments and future directions.

    abstract:INTRODUCTION:Despite the heterogeneity of prostate cancer (PCa), androgen stimulation is fundamental to its development, growth, and lethality. Therefore, the blockade of androgen receptor (AR) signaling is critical to controlling the disease, even after progression with castrate levels of androgens. AREAS COVERED:We ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2018.1513490

    authors: Isaacsson Velho P,Carducci MA

    更新日期:2018-10-01 00:00:00

  • Prostaglandin D2 receptor antagonists in early development as potential therapeutic options for asthma.

    abstract:INTRODUCTION:Asthma is a chronic inflammatory disease characterized by bronchial hyper-reactivity. Although many currently available treatment regimens are effective, poor symptom control and refractory severe disease still represent major unmet needs. In the last years, numerous molecular therapeutic targets that inte...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2016.1212838

    authors: Santus P,Radovanovic D

    更新日期:2016-09-01 00:00:00

  • VTX-1463, a novel TLR8 agonist for the treatment of allergic rhinitis.

    abstract:INTRODUCTION:Allergic rhinitis significantly impacts quality of life and current treatments are frequently unsatisfying. VTX-1463 is a potent, selective, Toll-like receptor (TLR) 8 agonist administered weekly via the intranasal route without concomitant administration of allergen for the treatment of allergic rhinitis....

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2011.583237

    authors: Horak F

    更新日期:2011-07-01 00:00:00

  • Investigational vasopressin receptor modulators in the pipeline.

    abstract::The vasopressin system is complex and interacts with the central nervous, cardiovascular, renal, and hematological systems. Vasopressin plays an important role in the control of blood osmolarity and vascular tone, but is also involved in many other physiological events, which are mediated mainly via three types of vas...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543780903066764

    authors: Favory R,Salgado DR,Vincent JL

    更新日期:2009-08-01 00:00:00