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This article is the original of Translational Medicine Network, please indicate the source for reprinting
Written by Jevin
On June 28, 2012, Professor Jennifer Doudna and others published an epoch-making paper
in Science.
The study revealed the detailed mechanism of action of the CRISPR-Cas system and pointed to its potential
as a genome editing tool.
On October 7, 2020, the official website of the Nobel Committee announced that Emmanuelle Charpentier and Jennifer Doudna were awarded the 2020 Nobel Prize in Chemistry for "developing genome editing methods
".
On November 23, 2022, a blockbuster study led by Professor Jennifer Doudna was published in Cell
.
The new study uncovered a large number of potential CRISPR-based gene editing tools
in thousands of viruses.
style="box-sizing: border-box;">Research background
01
The CRISPR-Cas system is best known as a genome editing tool, but it's actually a class of immune systems
that are widespread in nature.
40% of bacteria and 85% of archaea have the CRISPR-Cas system, and these prokaryotes can capture fragments of the genome of invading viruses or plasmids and store them in CRISPR arrays in their own
genomes.
When these viruses invade again, the CRISPR array acts as a template to transcribe RNA, directing the Cas enzyme to cut the corresponding DNA of the invading virus and thus defend against the invading virus
.
However, how many phages have evolved their own CRISPR-Cas system is unclear
.
Now, scientists have discovered new sources of CRISPR-based genome editing tools that promise to inspire new biotechnologies
.
Research process
02
Using metagenomic analysis of microbial samples isolated from soil, aquatic, human and animal microbiomes, Professor Jennifer Doudna's team reported the diversification encoded in the phage genome, and they found about 6,000 bacteriophages with the CRISPR-Cas system (0.
4% of known phages), covering all six known CRSIPR-Cas system types (types I-VI, e.
g.
Cas9 belongs to type II.
and Cas12 belongs to type V, Cas13 belongs to type VI).
Bacteriophage and phage-like sequences lead to several times the amplification of CRISPR-Cas9 and -Cas12 enzymes belonging to the type II and V families, which are widely used in genome editing applications
.
Casλ is the most distinct of the bacteriophage-coding V-type enzyme sequences identified in the study and was found to be potent biochemical as
an RNA-guided double-stranded DNA cutter.
Its molecular structure determined by cryo-electron microscopy explains its use of native monoguide RNA for DNA binding, and cell-based experiments demonstrate robust endogenous genome editing activity
in plant and human cells.
The compact structure of Casλ and other bacteriophage-encoded CRISPR-Cas proteins holds significant promise for carrier-based and direct delivery into cells for a wide range of biotechnology applications
.
That is, Casλ enzymes from bacteriophages (type V, just over 700 amino acids in size) can edit plant (Arabidopsis, wheat) and human cell genomes with the advantages
of miniaturization and high editing efficiency.
These findings suggest that viruses (bacteriophages) are an important source for the discovery of
novel gene-editing tools.
Research significance
03
The study revealed that the CRISPR pathways encoded in different phages are ultra-compact antiviral systems, and the phage-encoded CRISPR system covers all known CRISPR-Cas types
.
Casλ uses uniquely structured CRISPR RNA (crRNA) to recognize double-stranded DNA
.
Casλ-RNA-DNA structure determined by cryo-electron microscopy reveals a compact bilobar structure capable of inducing genome editing
in mammalian, Arabidopsis, and hexaploid wheat cells.
The findings reveal a new source of CRISPR-Cas enzymes in bacteriophages and underscore their value
as genome editors in plant and human cells.
Resources:
style="white-space: normal;box-sizing: border-box;">Note: This article is intended to introduce the progress of medical research and cannot be used as a reference
for treatment options.
If you need health guidance, please go to a regular hospital
.
(Click above to view the detailed schedule)
