Exiqon
Home Search Contact Print
0 items in basket0
Sign In
 
 
Products Services Applications Resource Center Ordering About Exiqon
microRNA Research
lncRNA Research
mRNA Research
DNA Research
Custom Oligos
Other Reagents
RNA Isolation
Sequencing
Microarray Analysis
Real-time PCR
Northern Blotting
In Situ Hybridization
Functional Analysis
RNA Preparation
Sequencing
Microarray analysis
Real-time PCR
In Situ Hybridization
Antisense
RNA Preparation
Sequencing
Microarray analysis
Real-time PCR
In Situ Hybridization
Antisense
SNP Detection
Sequencing
Microarray Analysis
In Situ Hybridization
LNA Phosphoramidites
A2 Quencher
RNA Isolation Services
microRNA PCR Services
Sequencing Services
XploreRNA
microRNA ISH Services
Custom Pharma Service
Isolation
Microarray Analysis
Northern Blotting
Real-time PCR
In Situ Hybridization
Functional Analysis
SNP Detection
RNA
microRNA
RNA
DNA
microRNA
microRNA
RNA
microRNA
RNA
DNA
microRNA
RNA
DNA
microRNA Resources
mRNA and lncRNA Resources
Documents
Reading rooms
Application Stories
Technology
Oligo design tools
Movies
microRNA
Research Guide
Reading rooms
Application Stories
Bioinformatics and data analysis
What are lncRNAs?
Application Stories
Bioinformatics
Oligo modifications
LNA™
AQ-link
Order microRNA products
Order custom oligos
Distributors
Global Service Providers
General Information
Contact
News
History
Management
Board of Directors
Newsletter
Career
Sign up to Newsletter
Newsletter Back Issues
 

In vivo LNA™ microRNA Inhibitors

miRCURY LNA™ In vivo microRNA Inhibitors are quietly revolutionizing the microRNA field by enabling functional analysis in live animal models.


microRNAs in human disease

Cancer, heart disease and metabolic disorders such as diabetes are some of the most common causes of human deaths. Recent publications in Nature and Cell using in vivo inhibition of microRNAs indicate that these small regulators of transcription may have great potential as therapeutic targets for these important diseases.

Read more
  • Extremely potent knockdown of microRNAs in broad range of tissues
  • Enables the discovery of surprising microRNA functions in live animals
  • Custom designed and highly purified
  • Superior serum stability and nuclease resistance

Superior in vivo LNA™ microRNA inhibitors

Effective microRNA inhibition has been achieved in multiple organs and tissues by systemic and local administration of custom designed in vivo LNA™ microRNA Inhibitors (Figure 1). As a result, surprising discoveries about microRNA function have been made that could not have been derived from cell culture experiments. Successful phase 2 human trials with a LNA™ miR-122 inhibitor for treatment HCV infections are a testimony to the unique drug like properties of these short antisense molecules1.


Product description

The in vivo LNA™ microRNA Inhibitors are highly purified custom designed microRNA inhibitors optimized for in vivo use. We exploit LNA™ technology maximally by designing short (14-16mer) inhibitors with fully modified PS backbone in order to optimize the pharmacokinetic and pharmacodynamic properties and to minimize toxicity. As an added benefit, the in vivo LNA™ microRNA are easily taken-up without the need for cholestrol-conjungation.

The high affinity of the LNA™-enhanced in vivo microRNA inhibitors makes them highly effective at physiological temperatures and when used in low concentrations, thereby minimizing potetional secondary effects not related to the antisense activity of the microRNA inhibitor. In addition, LNA™ incorporation enhances serum and nuclease stability.

The in vivo inhibitors are available with fluorescein and other custom modifications, in amounts ranging from 5 mg to kg scales. They are delivered dried down in Na salt ready to be dissolved in PBS. If needed, they can be delivered in the quality and with the documentation required for preclinical toxicity studies and human trials.

All in vivo LNA™ microRNA Inhibitors are designed upon request specifically for your microRNA target of interest. Please contact us for further information and ordering.


1. Janssen et al. Treatment of HCV infection by targeting microRNA. N Engl J Med. (2013) 368, 1685-94


Figure 1
Successful inhibition of microRNAs in a variety of tissues . (Click to learn more)

Extremely potent and well-referenced in vivo LNA™ microRNA inhibitors with low toxicity

LNA™ oligonucleotides have higher affinity for their targets than regular DNA or RNA based oligonucleotides. The LNA™ technology has been successfully applied in vivo, combining low concentrations of the microRNA inhibitor with high serum stability and low toxicity. in vivo miRCURY LNA™ microRNA inhibitors are so potent that effective microRNA inhibition has been achieved with buffered saline oligonucleotide solutions in a broad range of organs and tissues (Figure 1).


Effective knockdown in a broad range of animals by simple administration routes

in vivo LNA™ microRNA inhibitors have been used successfully in various animal models – small rodents, primates and even in humans. No special formulation or packaging in nanoparticles or lipid based transfection reagent is required. The most frequently used routes of administration are intravenous (through the tail vein in mice), intraperitoneal and subcutaneous. All three methods give similar biodistribution with most of the oligonucleotide accumulating in the liver and kidney. In general, we recommend subcutaneous administration because it is easy and can be repeated many times and in addition this method is associated with little discomfort to the treated animals.


Administer at low doses down to 5 mg/kg

The required dose regime varies with the target organ and animal model. In mice reported dose regimes range from 5-25mg/kg once or twice per week. Different types of local administration have been used successfully, such as oropharyngeal intratracheal instillation (lungs) and retro-orbital administration (eye). Oligonucleotides do not normally cross the blood-brain barrier and delivery to the brain requires intercranial surgery or alternatively administration into the cerebrospinal fluid.


List of selected scientific publications with in vivo miRCURY LNA™ microRNA Inhibitors:

Bhagat et al. miR-21 mediates hematopoietic suppression in MDS by activatingTGF-β signaling. Blood. 2013, 121(15):2875-81.

Boon et al. MicroRNA-34a regulates cardiac ageing and function. Nature. 2013, 495(7439):107-10.

Hollander et al. Striatal microRNA controls cocaine intake through CREB signalling. Nature. 2010, 466(7303):197-202.

Kornfeld et al. Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. Nature. 2013, 494(7435):111-5.

Ng et al. A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration. J Clin Invest. 2012, 122(3):1097-108.

Pencheva et al. Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell. 2012, 151(5):1068-82.

Seeger et al. Long-term inhibition of miR-21 leads to reduction of obesity in db/db mice. Obesity (Silver Spring). 2014, 22(11):2352-60.

Sene et al. Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Cell Metab. 2013, 17(4):549-61.

Son et al. The atypical mechanosensitive microRNA-712 derived from pre-ribosomal RNA induces endothelial inflammation and atherosclerosis, Nat Commun. 2013, 4:3000. PMID: 24346612



Figure 1
Successful inhibition of microRNAs in a variety of tissues . (Click to learn more)
Stefanie Dimmeler

MicroRNAs in heart disease


"The LNA™-inhibitors from Exiqon just work."

Stefanie Dimmeler, Professor and group leader, and Reinier Boon, Post Doctoral researcher, work in the Institute for Cardiovascular Regeneration at the Goethe University Frankfurt, Germany. Here they study the basic mechanisms underlying cardiovascular disease and vessel growth with the aim to develop new therapies to improve treatment of cardiovascular diseases.

Read full story...

Dr. Kiran Kumar Bali

microRNAs in pain


"I recommend Exiqon's miRNA inhibitors mainly because of their specificity and less off-target effects. Customer friendly handling of orders and providing useful discussions with experienced scientists is another reason for my recommendation."

Dr. Kiran Kumar Bali is a postdoc in Prof. Rohini Kuner's lab at the University Clinic Heidelberg in Germany. He has been using microRNA inhibitors in vivo to study microRNAs involved in chronic pain.

Read full story...

Jan-Wilhelm Kornfeld

microRNA and diabetes


"The rapid generation and delivery of LNA™ microRNA inhibitors allowed for the quick execution of in vivo experiments and offered an attractive alternative to the generation of conventional microRNA knockout models.The addition, the LNA™ inhibitors are highly effective"

Dr. Jan-Wilhelm Kornfeld works in the lab of Prof. Jens C. Brüning in the Department of Mouse Genetics and Metabolism at the University of Cologne and the Max-Planck-Institute for Neurological Research (MPI-nF). Their work using in vivo LNA™ microRNA inhibitors towards miR-802 in mice demonstrates the great future potential for oligonucleotide-based therapeutics for this complex disease.

Read full story...

David C. Henshall

MicroRNAs in epilepsy


"For us the main benefits of Exiqon’s microRNA inhibitors have been potency and high stability."

Eva M. Jimenez-Mateos and David C. Henshall work at the Centre for the Study of Neurological Disorders at the Royal College of Surgeons in Ireland. Here, they study how microRNAs influence epilepsy. A main challenge in the project was finding the optimal dose of inhibitor and scramble control to get specific inhibition and avoid off-target effects.

Read full story...

Holger Willenbring

The role of miR-21 in liver regeneration


Holger Willenbring, Associate professor and Raymond Ng, PhD student, from Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research Department of Surgery, Division of Transplantation at the University of California San Francisco study many aspects of liver regeneration. They have been using Exiqon array services and miRCURY LNA™ microRNA in vivo inhibitors to study the role of miRNAs in this process.

Read full story...

Please contact us for further information and ordering.
Our global technical support team will respond within 2 business days.
  Privacy   Sitemap   Legal