Gene Edits for Treatment of Disease

The fourth installment of our blog series about gene editing focuses on gene edits and editing for research purposes. We hope you that you find it informative – please Contact Us with any comments! View the other posts in this series!

Gene: A specific sequence of A, C, G, T units that instruct the sequence of amino acids that comprise a specific protein. Humans have 20- to 25 thousand genes

As part of our ongoing blog series about gene editing techniques and uses, the Bedford Research Foundation presents:

Gene Edits for Treatment of Disease

Most scientists have applied the CRISPR/Cas system to specific tissues or to stem cells. For example, it is theoretically possible to repair the X-chromosome mutations in liver cells so normal blood clotting factors can be produced by the liver.

CRISPR/Cas: “Clustered Regularly Interspaced Short Palindromic Repeats” is a term that describes DNA sequences in the viruses that infect bacteria. The immune system of bacteria includes a family of proteins (CRISPR-associated, Cas) that recognize CRISPR sequences and degrades them. The enzyme, Cas, needs to bind to a specific RNA sequence of 120 units, which can be synthesized synthetically, in order to degrade the DNA. These two components also function well in cell types other than bacteria, and so have become a useful tool for cutting DNA, resulting in either small deletions, or successful insertions of new synthetic DNAs. Both outcomes create an edited (mutated) gene.

Bedford Research scientists are applying the technology to edit B2M gene sequences in unfertilized eggs which are subsequently activated for stem cell derivation.

Gene edit: A modification of a specific sequence of A, C, G, T units that instruct the sequence of amino acids that comprise a specific protein. The edit may or may not alter the amino acid sequence and the protein.

But more recently other scientists have applied CRISPR/Cas technology to human embryos. Last year a Portland Oregon research team reported their efforts to repair a mutation in the gene MYBPC3 known to be associated with acute heart failure in young men. The 30-member team created embryos with sperm from a man carrying the mutated gene in half of his sperm. (It is important to note that this experiment is not possible in Massachusetts because the stem cell bill (MGLc 111L) specifically prohibits the creation of embryos for research purposes only.)

At the time of fertilization of eggs with the mutant sperm, the Oregon scientists also injected the CRISPR/Cas agents designed to home to the gene mutation and insert “normal” DNA sequences. They reported the repair was successful in some embryos, but not all. Other research teams in New York and Australia replied to the report with their own interpretations of the results and all groups agreed much more work is needed to understand how to reliably edit genes in early human embryos.

We cannot put this genie back in the bottle, but with reasoned approaches, humans can optimize the benefits and mitigate the dangers posed by gene editing. Many organizations are using this technology to find solutions for diseases, such as:

The Bedford Research Foundation is using CRISPR/Cas to further HIV prevention work using early Parthenote egg cells – More about our work is posted here.

Thank you for reading, please come back again next month for our posting on “Gene Edits for Enhancement”.

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