Step Aside, CRISPR: RNA Editing is Taking Off

Step Aside, CRISPR: RNA Editing is Taking Off

Publication date: Feb 06, 2020

In 2012, his team at the University of TcFCbingen in Germany discovered that by linking enzymes to engineered strands of RNA, they could change the sequences of messenger RNA molecules in cells.

RNA editing, by contrast, could allow clinicians to make temporary fixes that eliminate mutations in proteins, halt their production or change the way that they work in specific organs and tissues.

Several hurdles remain: current technologies can alter RNA sequences in only a few limited ways, and getting the system to work as intended in the human body will prove challenging.

Still, researchers hope that new technologies, such as protein engineering, and improved methods for delivering RNA to cells can help to overcome these limitations.

A foundational tenet in molecular genetics-its central dogma-was that cellular machinery faithfully transcribes genetic information from a double-stranded DNA template into a single-stranded RNA messenger, which is then translated into a protein.

Some have speculated that the ADAR proteins evolved as a defence against viruses, but many viruses with double-stranded RNA are unaffected by the enzymes.

It seems that highly intelligent cephalopods, such as squid, cuttlefish and octopuses, use RNA editing extensively to adjust genes involved in nerve-cell development and signal transmission.

No other animals are known to use RNA editing in this way.

A similar fate, he learnt, had befallen the work of researchers at a company called Ribozyme, who in 1995 proposed ‘therapeutic editing’ of mutated RNA sequences by inserting complementary sequences into frog embryos and allowing ADARs to edit the resulting double-stranded molecule and correct the mutation.

Peter Beal, a chemist at the University of California, Davis, says that the 2016 publication of the molecular structure of ADAR bound to double-stranded RNA made the system more understandable and enabled scientists to better engineer the enzyme to enhance its delivery or make it more efficient.

Many see RNA editing as an important alternative to DNA editing using techniques such as CRISPR.

Rosenthal expects, moreover, that RNA editing will prove useful for diseases without a genetic origin.

Permanently changing the Nav1. 7 gene through DNA editing could eliminate the ability to feel pain and disrupt other necessary functions of the protein in the nervous system, but tuning it down through RNA editing in select tissues for a limited amount of time could help to alleviate pain without the risk of dependency or addiction associated with conventional painkillers.

Although the system edited only a small amount of the RNA encoding dystrophin, it restored the protein to about 5% of its normal level in the animals’ muscle tissue, an amount that has shown therapeutic potential.

Concepts Keywords
ADAR Biotechnology
Addiction Cas9
Adenosine RNA interference
Adenosines ADAR
Bacteria Immune system
Beal CRISPR
Biochemist Genome editing
Bioengineer RNA splicing
Biological Engineer Biotechnology
Biologist Gene expression
Biotech Nucleic acids
Blood Diseases Branches of biology
Boston Dysfunctional protein haemophilia
Brain Pain
California Muscular dystrophy
Cambridge Chemical modifications
Cas9 Dogmawas cellular machinery
Cell Signal Laboratory applications
Cell Signalling Molecule translation machinery
Cephalopods Biotechnology
Chemist
Cholesterol
Conscripted
CRISPR
Cuttlefish
Cystic Fibrosis
Cytosine
DNA
Dystrophin
Embryonic Development
Engineering
Enzyme
Faithfully
FDA
Frog
Gene
Genetic
Genetic Mutation
Genetic Variant
Genetically Modified
Geneticist
Genome
Germany
Guanosine
Haemophilia
Heidelberg
Immune Reaction
Immune System
Immunologist
Inosine
Jin
Leiden
Mali
Marine
Marine Biological Laboratory
Massachusetts
MIT
Molecule
Motor Neuron
MRNA
MRNAs
Muscle
Muscular Dystrophy
Mutation
Nanoparticle
Nervous System
Netherlands
Octopuses
Pain
Painkillers
Protein
Protein Translation
Pseudouridylation
Puerto Rico
Retinal Disorders
Ribozyme
RNA
RNA Editing
RNAi
Rochester
Salt Lake City
San Diego
San Juan
Scissors
Scopus
Sodium Channel
Squid
Stanford
Syndrome
Tao
The Corrections
Tumour
Tuning
Uridine
Utah
Virus
Viruses
Woods Hole

Semantics

Type Source Name
drug DRUGBANK Tricyclazole
disease MESH blood diseases
disease MESH eye disease
disease MESH cystic fibrosis
drug DRUGBANK Troleandomycin
drug DRUGBANK Uridine
disease MESH haemophilia
disease MESH Cancer
drug DRUGBANK Cholesterol
drug DRUGBANK Tropicamide
disease MESH genetic diseases
disease MESH muscular dystrophy
drug DRUGBANK Adenosine
drug DRUGBANK Inosine
drug DRUGBANK Guanosine
disease MESH development

Similar

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *