CRISPR/Cas9

Out of the Clinic and Into the Lab

Visiting Medical Students Look Back on IRP Research Experience

Alex Valenzuela

When patients are affected by complex and poorly understood medical problems, it can only be an advantage when their doctors have one foot in the exam room and another in a laboratory studying the disease. However, physicians don’t accrue scientific skills on their own. Rather, they often must venture outside of their medical education to gain experience in research via programs like NIH’s Medical Research Scholars Program (MRSP).

The MRSP allows medical students from across the United States to spend a year working in IRP labs alongside seasoned scientists. The 50 medical students and one dental student selected as 2022 Medical Research Scholars recently finished their time at NIH after arriving on campus last July. Between classes, clinical rounds, study sessions, and exams, five of those young men and women found the time to describe their experience at NIH to the “I Am Intramural” blog, so read on to get a taste of what the MRSP has to offer our nation’s aspiring physicians.

IRP’s Eugene Koonin Elected to National Academy of Medicine

Scientist Decoded DNA to Build a Genomic Tree of Life

Dr. Eugene Koonin

In 1973, the geneticist Theodosius Dobzhansky wrote a now-famous essay that declared, “Nothing in biology makes sense except in the light of evolution.” That sentiment has served as the guiding principle for the career of IRP senior investigator Eugene V. Koonin, Ph.D., who was elected to the National Academy of Medicine (NAM) in October 2022 for his contributions to the field of evolutionary biology.

Dr. Koonin’s pioneering efforts to identify clusters of similar genes found in different organisms passed down by a common ancestor — known as ‘homologous’ genes — has helped to unlock the secrets encoded in DNA and create a foundation for the systematic study of how genes evolve and function. His lab at the National Library of Medicine’s National Center for Biotechnology Information (NCBI) uses a combination of genomic sequencing and mathematical modeling to compare genes across species and determine how they work and where they came from. From this information, his team can develop a systematic framework to show the relationship between genes as they evolved. It’s like drawing the tree of life, but on a genomic scale.

IRP’s Andre Nussenzweig Elected to National Academy of Medicine

NIH Researcher Recognized for Investigation into Genomic Stability

Dr. Andre Nussenzweig

The National Academy of Medicine (NAM), first established in 1970 by the National Academy of Sciences as the Institute of Medicine (IOM), is comprised of more than 2,000 elected members from around the world who provide scientific and policy guidance on important matters relating to human health. Election to the NAM is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have not only made critical scientific discoveries but have also demonstrated a laudable commitment to public service.

IRP senior investigator Andre Nussenzweig, Ph.D., was one of four IRP researchers recently elected to the NAM. Dr. Nussenzweig leads the Laboratory of Genome Integrity at the National Cancer Institute (NCI), where he studies how cells repair a form of DNA damage called a double strand break (DSB). This type of insult, which severs both strands of the double-stranded DNA molecule, is one of the most dangerous. If not repaired properly, DSBs can kill cells or cause DNA to rearrange in ways that are associated with cancer. Moreover, while DSBs can be caused by chemotherapy drugs and radiation, they can also happen by random chance during the course of normal cellular processes. Intriguingly, not all parts of the DNA molecule are equally susceptible to this form of damage.

Gene Editing Reveals Potential Cancer Treatment Target

Scientists Parse Wide-Ranging Effects of Endometrial Cancer Mutation

a piece of DNA being removed from a DNA molecule

The so-called ‘butterfly effect’ supposes that a butterfly flapping its wings in Brazil can cause a tornado in Texas. While the jury is still out on insect-induced natural disasters, it is clear that a single genetic mutation can have wide-ranging and unexpected consequences throughout a cell. By examining the ripple effects caused by changes in a particular gene, IRP researchers have identified a potential treatment target for a particularly deadly variety of cancer.

Cutting-Edge Technique Simultaneously Edits Multiple Genetic Targets

Alternative to CRISPR/Cas9 May Cause Fewer Undesired Changes

diagram of DNA strand

IRP researchers have always worked on the cutting edge of biomedical science, from testing the first successful treatment for childhood schizophrenia to pioneering the first screening technique for HIV. In a new study, an IRP team recently achieved yet another first: simultaneously editing two genetic sites in mice using a brand-new approach called base editing that may prove to be more precise – and therefore safer – than other gene editing methods.

CRISPR Pioneer Jennifer Doudna Headlines NHGRI 25th Anniversary Celebration

It seems like every day there is a new story in a prominent news outlet about the revolutionary gene-editing approach known as CRISPR/Cas9. What these reports often fail to mention is all the scientific discoveries that paved the way for that groundbreaking technology, including the key contributions of government scientists working in the Intramural Research Program of NIH’s National Human Genome Research Institute (NHGRI). Last week, the NHGRI IRP celebrated its 25th anniversary with a day-long symposium headlined by a keynote from the co-discoverer of CRISPR/Cas9, University of California, Berkeley professor Dr. Jennifer Doudna.

Dr. Jennifer Doudna

Twitter Chat Shines Spotlight on Rare Diseases

Between 25 and 30 million Americans have a rare disease, defined as a condition affecting fewer than 200,000 people. On March 1, the NIH will host its annual Rare Disease Day to increase awareness of these under-recognized and often undiagnosed illnesses and highlight the efforts of scientists, patients, and advocates to produce treatments.

In anticipation of the occasion, on February 23, NIH organized a Twitter chat with NIH Director Francis Collins, M.D., Ph.D., and Sharon Terry, President and CEO of Genetic Alliance and a member of the Research Program Advisory Panel for NIH’s All of US project. Check out some of the more noteworthy exchanges below or look at the full Twitter chat by searching for #NIHchat on Twitter.

NIH Rare Disease Day logo

Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

Reblogged from the NIH Director’s Blog.

This image represents an infection-fighting cell called a neutrophil. In this artist’s rendering, the DNA of a cell is being “edited” with a pen-like tool to help restore its ability to fight bacterial invaders.

For gene therapy research, the perennial challenge has been devising a reliable way to insert safely a working copy of a gene into relevant cells that can take over for a faulty one. But with the recent discovery of powerful gene editing tools, the landscape of opportunity is starting to change. Instead of threading the needle through the cell membrane with a bulky gene, researchers are starting to design ways to apply these tools in the nucleus—to edit out the disease-causing error in a gene and allow it to work correctly.