Gene Editing & Research – Dr. Alejandro "Alex" Chavez, MD, PhD, Assistant Professor of Pathology and Cell Biology, Columbia University – Using CRISPR-Cas9 Technology to Edit Genes and Understand the Biology of Disease

Dr. Alejandro "Alex" Chavez, MD, PhD, assistant professor of pathology and cell biology at Columbia University, provides a detailed overview of the advances in CRISPR/Cas9 technology. CRISPR/Cas9 is a genome protection system utilized by many microbes to prevent foreign DNA and nucleic acids from infiltrating their genomes and potentially causing damage. Gene editing (changing the sequence of DNA) is not a new development, but the CRISPR/Cas9 technology allows for greater efficiency with gene editing at a lowered cost. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and the Cas9 essentially acts, as Dr. Chavez states, like a targeted missile. It works by taking small pieces of a genome and utilizing Cas9 to target or hunt down other copies of the sequence. As researchers learned more, the push to increase human gene editing, to target and attack specific genes reached an intense demand, for the potential for medical and scientific breakthroughs is immense. As Chavez explains, once Cas9 learns that a particular sequence belongs to a virus it will then seek it out, bind to it, and cut it, thus rendering it ineffectual. And as the defense effect takes hold, it strengthens other DNA in a system increasing resistance overall. Dr. Chavez discusses how the use of Cas9 has to be extremely specific, as Cas9 is so hard-working that it's essential that it be carefully planned so as to attack only the intended target. The cell biology expert provides an overview of restriction enzymes and the targeting and cutting of DNA. As he states, with CRIPSR, researchers can target literally anything they want, making it more efficient in research as a precision tool. Dr. Chavez explains the remarkable possibilities that CRISPR technology has created, as it can be utilized to turn single genes off, one by one, to see what happens, thus allowing for a systematic pattern of research. But as CRISPR is excellent at cutting genes off, there hasn't been an easy way to use CRISPR to turn genes on, so as the cell biology professor explains, their research features study in this area. He expresses the importance of seeing the gene in various ways, to have two different pictures of what the gene is doing. Chavez's lab built a tool that allows researchers to use CRISPR to turn genes on, which gives researchers a deeper look into the gene's actions and how it works. Chavez discusses Cas9 variants in terms of how they are utilized, their specificities, and how they cut DNA. He explains that while the variations are many, most researchers use Streptococcus pyogenes Cas9 (SpCas9) due to its overall efficiency, for as Chavez states, it's a jack of all trades. The genome researcher provides information on some future developments on the horizon, such as in vivo recorders that make physical copies of events within the genome, and the packaging of CRISPR for sterilization in medical procedures. Additionally, he explains how CRISPR specificity can allow more targeted cutting such that an exact area can be cut to specifically kill only the part of a bacterium that is harmful. With the advances in CRISPR, Chavez's lab is diving deeper into study of neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as others, to understand the biology of diseases.