But CRISPR requires both a pair of molecular “scissors” borrowed from bacteria and a separate cut-and-paste function to insert the desired edit. This two-step process restricts the length of genetic material CRISPR can tweak.
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CRISPR is also prone to making off-target edits,introducing unwanted and potentially dangerous mutations into the DNA. Whenever you cut DNA,you risk inflicting genetic damage that can turn carcinogenic.
The Australian scientists’ new technique,called seekRNA,can elegantly perform the genetic cut-and-paste all in one go,says Ataide’s colleague and lead author of theNature Communicationspaper Rezwan Siddiquee,thus slashing the chance of off-target mutations.
“It can both cut DNA and paste DNA,all in one system,” Siddiquee says. “So you could essentially reprogram things in a much simpler way,and it’s exponentially more specific than CRISPR. It’s a total game changer in the editing field.”
‘Jumping genes’:How the new tool works
The team recruited the key RNA (which enables DNA to act as genetic instructions) from a particular family of “jumping genes” or transposase,segments of genetic material that move around on a genome.
The naturally nomadic genetic material latches onto extremely specific “target sites” on DNA strands.
Ataide and his team reprogrammed this system to make their precise edits to bacterial DNA. Because the seekRNA is a small,sleek package,the researchers believe their technique may be more easily delivered to cells,leading to research that could underpin new COVID-19 vaccines and bring down the multimillion-dollar cost of gene therapies.
“CRISPR is not a perfect tool. It can introduce undesired changes at times,” Doudna acknowledged at a Sydney Opera House talk last month. The new cutting-edge research in the field,she said,would be scientists finding ways to make CRISPR more efficient,cheaper and easier to deliver therapeutically.
Amid an international race to develop next-generation gene-editing tools,Ataide and his colleagues have applied to patent their technique and are embarking on the next phase of research:testing seekRNA within eukaryotic cells (the kind in plants,animals and humans). If that works,Siddiquee says,there is “unlimited potential here”.
Spicy tomatoes and illegal babies
CRISPR asa gene-editing tool burst on the scene about a decade ago,and it is relatively easy to use. We’re only at the start of teasing out its applications. Scientists are investigating uses for CRISPR as diverse as banishing the allergy-triggeringproteins from nuts,decaffeinating coffee beans,making spicy tomatoes and curing Dalmatians of bladder stones (the poor pups have a genetic predisposition for the affliction).
Gene editing could one day eliminate diseases such as type 1 diabetes andcystic fibrosis from the human population too. It also has a role in tackling climate change;Doudna isworking with Californian scientists trying to disable the bacterial genes that lead to cows belching and farting enormous amounts of methane,a greenhouse gas that significantly contributes to global warming.
But all that wonder comes with a warning. Doudna said she was “horrified” when,in 2018,Chinese scientist He Jiankui announced he had used CRISPR on two babies,twins nicknamed Lulu and Nana. He tweaked genes in their embryos he claimed would make them immune to HIV.
Jiankui waspromptly jailed. But since his release,he has been back in the lab working on CRISPR.
As the technology continues to become cheaper and more precise,we’ll see more of these controversies shadowing the vast scientific and medical promise of our new ability to rewrite the code to life.
The clear ethical line in Doudna’s mind is using CRISPR and other DNA-tweaking tools to make heritable edits to human genes.
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“When we’re talking about sickle cell disease,or these other applications of CRISPR,those are all uses of gene editing that affect one individual,” Doudna said. “They don’t create heritable changes that are passed on to future generations.
“But making edits in embryos or eggs or sperm does just that – it creates a heritable change that is passed on. Why is that problematic? Well,when you start to think about it,it makes you think of things like eugenics … possibly using CRISPR in ways that could create more inequities than we already have in the world.”
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