ABBIE in advancing drug discovery
Exciting news has emerged from the field of gene-editing technology with the first-ever approval of a treatment that utilizes CRISPR. Known as Exa-cel or Casgevy, this groundbreaking therapy has recently received regulatory approval from the U.K. Medicines and Healthcare products.
Regulatory Agency (MHRA) on November 16, 2023. Its primary objective is to address two debilitating blood disorders: sickle cell disease and transfusion-dependent beta-thalassemia.
Late in October, experts advising the U.S. Food and Drug Administration (FDA) determined that this gene-editing drug is safe for clinical use. The FDA itself is now expected to make its final decision regarding the approval of the treatment by December. This significant milestone is generating considerable anticipation within the scientific community and holds the potential to revolutionize the treatment of these life-altering conditions.
This exciting breakthrough in the gene therapy supports SOHM Inc’s efforts for introducing our novel gene editing technology, ABBIE (A Binding Based Integrase Enzyme) genome editing system, for safe integration of designed donor DNA sequences into the genome of a cell.
Establishment and acceptance of regulatory pathways for gene therapy provides clear direction for introduction of the ABBIE system in a seamless and streamlined manner allowing for a potential reduced time and cost for obtaining approval using our ABBIE system.
ABBIE differentiates from the CRISPR system by introducing DNA via a targeted integration mechanism and therefore does cause double stranded DNA breaks and importantly does not completely rely on cellular mechanisms of repair to generate an edit. In summary, the ABBIE system saves time and money by using an efficient mechanism of genetic delivery.
Through this ABBIE system, cells or animal models with various genetic and phenotypic
characteristics can be produced. Normal or disease genes, which differ genetically from the normal gene in a disease, can be inserted into a cell’s genome for investigation of their function and responses to treatments.
While genome editing is further researched for direct treatment and cure of human diseases, these systems are also being developed for agriculture, diagnostics and discovery of new drug targets.
In drug discovery, a researcher finds and validates novel pharmaceutical targets through drug screens. CRISPR has been utilized to find drug targets through knocking out gene function in large scale screens. This has resulted in finding new drug targets for treating diseases such as cancer. For example, ZMYND8, an epigenetic regulatory protein, was recently found as a target to treat acute myeloid leukemia (AML) through a CRISPR screen. Promising novel targets were also found for multiple myeloma in a CRISPR screening.
There are five steps in advancing drugs to clinical studies: target identification and validation, compound screening, hit validation, lead identification and optimizing, and clinical trials. In target
identification and validation, large scale loss of and gain of function studies are conducted in order to find possible targets for drug treatment. The discovered targets are then validated to find the best candidates. Next compounds are screened based on validated targets to find compounds to further confirm. Screening of the active compounds will produce one or more lead compounds that are optimized for ideal effective concentration, safety and mode of delivery. Once the leads are optimized, the lead compounds will be moved into clinical studies.
SOHM envisions ABBIE in a system to quickly edit cells for drug screens. Cells can be engineered with ABBIE for expression of various drug targets such as receptors, kinases, cellular enzymes and other cellular proteins in normal and disease forms. These cells will better model in vivo disease mutations found in humans and can be used to find pharmacological targets and will be used in drug screens to identify lead compounds for a multitude of diseases.
The ABBIE screening system will be able to identify new therapeutic uses for new and existing drugs.