Context (TP): A naturally occurring human DNA editing tool was discovered.
Significance of the discovery
This next-generation genomic design method is called the bridge recombinase mechanism.
It utilises jumping gene IS110, which cuts and pastes itself into genomes and is present in all life forms, performing on-the-go DNA manipulation through all living beings.
The bacteria used in the study, E. coli, have a lot of IS110 sequences. They roam around the body, cutting and pasting themselves, repairing DNA, and modifying it daily.
Beyond RNA interference and CRISPR, the diversity of nucleic-acid-guided systems is increased by the IS110 bridge recombination mechanism.
The role of jumping genes as bridges
Jumping genes randomly jump from one site to another, inserting genetic information as they go, using enzymes called transposases. It can slide into the DNA to insert or integrate without cuts.
A guide can be used to efficiently program the jumping gene, which can then precisely insert itself into user-defined genomic locations.
These Jumping genes are minimal segments of DNA with the recombinase enzyme, which binds this DNA to other DNA, along with extra DNA.
This extra DNA at the ends of jumping genes gets joined together and converts the DNA double helix structure into a single-stranded RNA molecule that folds into two loops.
After that, each element loop can bind to the donor and target segments of DNA individually. This can then attach to two sets of DNAs: the donor and the target.
When inserting or recombining sequences into DNA, there is tremendous freedom because the donor and target loops can be individually programmed.
CRISPR-Cas9
CRISPR-Cas9 is a technology that allows the modification, addition, or removal of specific DNA sequences, changing genome portions.
The CRISPR-Cas9 system consists of two key molecules that introduce a change in the DNA. These are
Cas9 enzyme: acts as a pair of ‘molecular scissors’ that can cut the two strands of DNA at a specific location in the genome so that bits of DNA can be added or removed.
Guide RNA (gRNA): A piece of pre-designed RNA sequence located within a longer RNA scaffold.
The scaffold part bindstoDNA, and the pre-designed sequence ‘guides’ Cas9 to the correct part of the genome. This ensures that the Cas9 enzyme cuts at the right point in the genome.
The purpose of the guide RNA is to locate and bind to a particular DNA sequence.
The target DNA sequence in the genome and the guide RNA have complementary RNA bases.
This implies that the guide RNA will only, at least in principle, bind to the target sequence and not to any other parts of the genome.
The Cas9 follows the guide RNA to the same location in the DNA sequence and cuts across both strands.
At this stage, the cell recognises that the DNA is damaged and tries to repair it.
Scientists can use DNA repair machinery to introduce changes to one or more genes in the genome of a cell of interest.
How RNA bridge differs from CRISPR ?
RNA bridge
CRISPR
Consists of a recombinase protein that hooks up with a guide RNA, like the CRISPR Cas9.
Unlike CRISPR, the guide RNA specifies two DNA sequences to seek out, not just one.
One sequence specifies the target site in the genome to be altered, just as in CRISPR.
The other specifies the DNA to be altered. This system can add, delete, or reverse DNA sequences of virtually any length.
There are two parts to the standard CRISPR Cas9 protein.
One part links with a guide RNA molecule and seeks out any DNA that matches a certain section of the guide RNA.
The second part of CRISPR Cas9 is a cutter that severs DNA once the Cas9 has bound to its target site.
