Hello fellow biotech lovers!
In May of this year, you might have heard the incredible news that researchers from
Temple University have, for the first time in history, successfully removed the AIDS-causing
HIV-1 DNA from the genome of living animals!
What extraordinary technology made this breakthrough possible?
CRISPR Cas9, of course!
But, we're not talking about Cas9 derived from Streptococcus pyogenes that usually comes
to mind when we think of CRISPR.
We're talking about a more recently discovered "miniature" Cas9 from staphylococcus aureus
identified by MIT's Zhang team in collaboration with Harvard University and
the National Institute of Health.
This little nuclease has big potential to change the game in biomedical research by
making CRISPR-based gene editing in living organisms that much more feasible!
This is Molecular Minutes, bringing you breakthroughs at breakneck speeds.
In this video, we'll introduce you to saCas9, a nuclease that's making waves as a powerful
tool in gene therapy and one we're excited to say will be available soon, here at Applied
Biological Materials.
So, what's the deal with saCas9?
According to the original paper, published in April 2015 in Nature, saCas9 is the
only other known Cas9 nuclease that can target and cleave DNA in vivo with about the same efficiency
as spCas9.
In fact, there are only two major differences that set them apart from each other.
First, saCas9 has a different PAM sequence compared to spCas9.
And second, saCas9 is about ~1 kb smaller than spCas9!
If you've watched our last episode of Molecular Minutes about the CRISPR Cpf1 system, you'll
know that in gene therapy, great things come in small packages--packages about the size
of the adeno-associated virus, to be exact.
Scientists like using AAVs because they are non-pathogenic, don't trigger strong immune
responses, and allow for tissue-specific infection.
But, AAVs are like sports cars--they have great performance but limited space in the trunk!
Because AAVs can only fit 4.5 kb worth of DNA, spCas9 barely fits--if at all-- and definitely
doesn't leave any room for extra baggage such as regulatory expression elements which is
pretty inconvenient.
Because saCas9 is only ~3.3 kb, it fits snugly within the AAV vector and even allows for
one or two gRNAs to be included in the same construct!
So, how does saCas9 perform in vivo?
In the original Nature paper, the authors injected AAVs carrying saCas9 into mice to
disrupt the PCSK9 gene, a gene linked to high cholesterol and genetic conditions such as
familial hypercholesterolemia.
They saw an increase of 40% indel formation in liver tissue after only 1 week and no signs
of toxicity 4 weeks after injection.
In the more recent study done by Temple University scientists, saCas9 was able to remove the
HIV-1 DNA inside every tissue of transgenic mice only 2 weeks after injection.
Although it was later found that the HIV molecule was able to resist these first editing attempts,
the idea of using CRISPR to one day eradicate HIV is one that remains full of potential!
In fact, CRISPR-based medicine is so promising that Editas Medicine, the CRISPR-based therapeutics
company founded by Feng Zhang himself, is already experimenting with saCas9 to discover
new treatments for other diseases, such as Cystic Fibrosis.
There may soon be a time when personalized therapy can be delivered faster than you can say
"Search and Destroy".
Eager to get started with saCas9?
So are we!
That's why saCas9 will be available at abm very soon!
But, if you want to begin your gene editing adventures right now, we've got an entire
portfolio of CRISPR tools at your disposal, including our new CRISPR Knockout cell lines.
So, go knock yourself out!
Thanks for watching Molecular Minutes--stay tuned for more newsflashes as we follow the
latest movers and shakers in the biotech industry.