Since its discovery in 2012, the CRISPR-Cas9 gene-editing system has demonstrated unprecedented potential for the treatment of genetic diseases, cancers, and a multitude of other conditions. Working upon an ancient bacterial immune response system, CRISPR has the ability to act like a “cut-and-paste” tool to precisely edit out and replace bits of DNA in mammalian cells. This precision along with greater ease-of-use and lower cost compared to other gene-editing techniques, was the reason that in 2020, scientists Jennifer Doudna and Emmanuelle Carpentier earned the Nobel prize in Chemistry for their critical work in discovering the CRISPR-Cas9 system.
As revolutionary as this system is, a few limitations have been found with in vivo trials of CRISPR therapies, specifically in the way they are delivered. Most often, inert and non-replicating viruses are used to transport the components of the CRISPR system (DNA, mRNA, and proteins) into cells. Despite the effectiveness of this method and its lack of causing DNA integration, this method has also been known for the potential to have off-target effects which can reduce gene-editing efficiency.
A solution to this delivery method has come in the form of lipid-like nanoparticles called LNPs that maintain a high delivery rate without the adverse effects of viral approaches. However, when it comes to the treatment of certain cancers, a more tissue-specific approach is needed to improve efficiency of LNP-enabled CRISPR therapies. That is where new research in electrospun scaffolding has come in.
Researchers at Columbia University studying a bone marrow-associated form of leukemia called adult acute myeloid leukemia (AML), discovered a new way to improve tissue-specific uptake of CRISPR therapies using electrospinning. Acute myeloid leukemia, the leading form of leukemia, and the most deadly, causes the production of a large number of abnormal blood cells that disrupt normal bodily functions. This production is sustained by leukemia stem cells (LSCs) which can become resistant to chemotherapies and cause relapse.
To target these stem cells, researchers loaded what are known as ‘chemokines’ into an electrospun bone marrow-mimicking scaffold, injected at the cancer site. These chemokines attract the LSCs to the scaffold which was also coated with lipid-like nanoparticles containing CRISPR therapy components. Using this method, researchers were able to provide a more sustained delivery of the CRISPR-Cas9 therapy locally, increasing overall therapeutic efficacy.
Every day, advancements to drug deliveries like these are being made to improve patient outcomes and give individuals the right to choose a therapy that works for them. At Hera Health Solutions, our goal is to expand and demonstrate through action that drug delivery can be so much more than what it is today. Like finding synergy between CRISPR and electrospinning, Hera pushes the envelope of what is possible through nanofabrication and therapeutics. Our commitment to constantly innovate leads us to test the boundaries of nanotechnology and to explore ways to make drug delivery more efficient, safe, and convenient for all.