What is the Difference Between RNA Interference and Antisense Oligonucleotide

The key difference between RNA interference and antisense oligonucleotide is that RNA interference is a technique that involves sequence-specific suppression of gene expression by a double-stranded RNA while antisense oligonucleotide is a technique that involves sequence-specific suppression of gene expression by a single-stranded DNA oligonucleotide.

Gene silencing or suppression is a way of regulating gene expression in a biological cell to prevent the expression of a specific gene. Normally, when genes are silenced, their expression is reduced. In contrast, when genes are knocked out, they are completely erased from the genome of the organism; thus, will have no expression. Sometimes, gene silencing is considered the same as gene knockdown. This is because gene silencing methods such as RNAi, antisense oligonucleotide, and CRISPR that are used to silence genes cause a reduction of gene expression by at least 70%. RNA interferences and antisense oligonucleotides are two important gene silencing techniques.

CONTENTS

1. Overview and Key Difference
2. What is RNA Interference 
3. What is Antisense Oligonucleotide
4. Similarities – RNA Interference and Antisense Oligonucleotide
5. RNA Interference vs Antisense Oligonucleotide in Tabular Form
6. Summary – RNA Interference vs Antisense Oligonucleotide

What is RNA Interference?

RNA interference (RNAi) is a biological process in which double-stranded RNA molecules carry out sequence-specific suppression of gene expression. Andrew Fire and Craig C. Mello shared the Nobel prize in 2006 in Medicine for their exceptional work on RNA interference in nematode worm: Caenorhabditis elegans. This pioneering research on RNA interference was first published by them in 1998. Usually, the RNAi pathway is found in many eukaryotic organisms, including animals. 

Two central molecules, microRNA (miRNA) and small interference RNA (siRNA), are involved in the RNAi pathway. An enzyme called Dicer induces this pathway. Dicer cleaves long double-stranded RNA into short double-stranded fragments (21 nucleotides siRNA). Then each siRNA is unwound into two single-stranded RNAs known as passenger strand and guide strand. The passenger strand is degraded while the guide strand is incorporated into the RNA induced silencing complex (RISC). In the RISC, guide strand pairs with complementary mRNA, which triggers Argonaute (Ago2), the catalytic component of the RISC complex. Later, Argonaute cleaves the mRNA molecule. Unlike siRNA, the microRNA (miRNA) targets the 3’ untranslated region of mRNA where they bind with imperfect complementarity. This blocks access of mRNA to ribosomes for translation.

What is Antisense Oligonucleotide?

Antisense oligonucleotide is a technique that involves sequence-specific suppression of gene expression by a single-stranded DNA oligonucleotide. This technique is also called antisense therapy. It is a form of therapy that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). Antisense oligonucleotides alter the mRNA expression by using a variety of mechanisms such as ribonuclease H mediated decay of pre mRNA, direct steric blockage and modulation of exon content through splicing site binding on pre mRNA.

Several antisense oligonucleotides have been approved by the United States and European Union for disease treatment. Moreover, antisense oligonucleotides have already been approved as a therapy for many diseases including, Batten disease, cytomegalovirus retinitis, Duchenne muscular dystrophy, familial chylomicronaemia syndrome, familial hypercholesterolemia, hereditary transthyretin-mediated amyloidosis, and spinal muscular atrophy.

What are the Similarities Between RNA Interference and Antisense Oligonucleotide?

• RNA interference and antisense oligonucleotide are two important gene silencing techniques.
• Both techniques target mRNA molecules. 
• They are sequence-specific techniques. 
• Both techniques are used as therapies for many diseases. 
• They both inhibit gene expression.

What is the Difference Between RNA Interference and Antisense Oligonucleotide?

RNA interference is a technique that involves sequence-specific suppression of gene expression by a double-stranded RNA while antisense oligonucleotide is a technique that involves sequence-specific suppression of gene expression by a single-stranded DNA oligonucleotide. So, this is the key difference between RNA interference and antisense oligonucleotide.  

The below infographic presents the differences between RNA interference and antisense oligonucleotide in tabular form for side by side comparison.

Summary – RNA Interference vs Antisense Oligonucleotide

Gene silencing techniques reduce cellular gene expression. RNA interference and antisense oligonucleotide are two important gene silencing techniques. RNA interference is a technique that involves sequence-specific suppression of gene expression by a double-stranded RNA while antisense oligonucleotide is a technique that involves sequence-specific suppression of gene expression by a single-stranded DNA oligonucleotide. Thus, this summarizes the difference between RNA interference and antisense oligonucleotide.

Reference:

1. Agrawal, Neema, et al. “RNA Interference: Biology, Mechanism, and Applications.” Microbiology and Molecular Biology Reviews : MMBR, American Society for Microbiology, Dec. 2003.
2. Rinaldi, Carlo, and Matthew J. A. Wood. “Antisense Oligonucleotides: The next Frontier for Treatment of Neurological Disorders.” Nature News, Nature Publishing Group, 1 Dec. 2017.

Image Courtesy:

1. “Rna interference plos” By Marjori A. Matzke, Antonius J. M. Matzke – Matzke MA, Matzke AJM (2004) Planting the Seeds of a New Paradigm. PLoS Biol 2(5): e133 https://dx.doi.org/10.1371/journal.pbio.0020133 (CC BY 2.5) via Commons Wikimedia
2. “Antisense DNA oligonucleotide” By Robinson R – RNAi Therapeutics: How Likely, How Soon? Robinson R PLoS Biology Vol. 2, No. 1, e28 doi:10.1371/journal.pbio.0020028 (CC BY 2.5) via Commons Wikimedia