CRISPR revolutionized gene editing by enabling precise DNA modifications, leading to groundbreaking treatments for genetic disorders. Feng Zhang, a pioneer of CRISPR, is now exploring a new gene editing system called TIGR found in viruses and bacteria. TIGR may offer more powerful and versatile gene editing capabilities, potentially overcoming CRISPR's limitations and opening new frontiers in biotechnology and medicine.
CRISPR is widely regarded as one of the most transformative breakthroughs in biotechnology, comparable to the discovery of DNA's structure. In just over a decade, scientists have progressed from questioning whether CRISPR could work in humans to successfully rewriting the DNA of a living infant to administer a lifesaving treatment. However, CRISPR's origins were humble, rooted in curiosity about bacterial immune systems rather than a grand plan to cure genetic diseases.
Feng Zhang, a key figure in pioneering CRISPR gene editing in human cells, initially studied components of bacterial immune systems. His groundbreaking work helped establish CRISPR as a gene editing tool capable of targeting and modifying DNA sequences with unprecedented precision. Yet Zhang's scientific journey did not stop there. He has returned to the lab to investigate a newly discovered set of genes called TIGR, found in some viruses and single-celled organisms. This system may surpass CRISPR in certain gene editing applications.
Zhang's approach to science is deeply rooted in basic research—understanding fundamental biological mechanisms without immediate commercial applications. He believes that unexpected observations often lead to novel discoveries. His scientific curiosity was nurtured from childhood, influenced by his computer scientist parents who encouraged him to dismantle and understand complex systems.
His initial fascination with computers evolved into a passion for molecular biology during a seventh-grade enrichment class. He was captivated by the concept that DNA acts like a code, similar to computer programming, where altering the code changes how cells behave. This realization inspired him to explore gene editing as a way to rewrite the instructions of life.
In high school, Zhang volunteered at a gene therapy lab studying green fluorescent protein (GFP), a jellyfish protein that glows under certain conditions. GFP became a powerful tool to track proteins and study viral infections. For example, by tagging cancer cells with GFP, researchers can observe how cancer spreads in living organisms.
Zhang continued his studies at Harvard and Stanford, focusing on how viruses infect cells and replicate. In 2009, he returned to Harvard to experiment with gene editing techniques, leading to his work on CRISPR-Cas9.
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, a natural bacterial immune system that defends against viruses. It uses a guide RNA to locate specific DNA sequences and an enzyme called Cas9 to cut the DNA at targeted locations. This molecular "cut and paste" system allows scientists to edit genes precisely.
Other researchers, including Emmanuelle Charpentier and Jennifer Doudna, contributed to understanding CRISPR, earning a Nobel Prize for their work. Zhang was the first to adapt CRISPR-Cas9 for use in eukaryotic cells, including mice and humans.
Zhang and his team discovered and engineered various Cas proteins, such as Cas12a, which is smaller and requires only a single RNA guide, making it easier to deliver into cells. Cas12a also creates jagged cuts in DNA, which reduces mutation risks compared to the blunt cuts made by Cas9.
CRISPR has been investigated as a treatment for at least 18 disorders, including sickle cell anemia and leukemia. Typically, scientists edit cells outside the body and then reintroduce them to patients. In 2025, CRISPR was used for the first time to edit DNA directly inside a living infant, marking a milestone in gene therapy.
Despite its successes, CRISPR has limitations. It is most effective for diseases caused by single genetic mutations. Complex diseases involving multiple genes or unknown mutations are harder to treat with CRISPR. Additionally, delivering CRISPR components to all affected cells in the body remains a challenge.
These limitations motivated Zhang to explore alternative gene editing systems. His team discovered a new set of genes called TIGR (Tandem Interspaced Guide RNA), found primarily in viruses and some bacteria.
TIGR consists of repetitive DNA sequences interspersed with unique guide RNA sequences that direct the system to specific DNA targets. Similar to CRISPR, TIGR includes proteins capable of cutting DNA. However, TIGR is mostly found in viruses, which raises intriguing questions about its biological role.
Viruses are simple organisms, so the presence of such a sophisticated DNA targeting system suggests it may play a role in viral and bacterial interactions. One hypothesis is that viruses use TIGR to insert their DNA into bacterial genomes, while bacteria might use it to defend against viral infections.
Zhang's ongoing research into TIGR aims to understand its mechanisms and potential as a gene editing tool. If TIGR proves more versatile or efficient than CRISPR, it could revolutionize gene editing further, enabling treatments for a broader range of diseases and improving delivery methods.
The discovery of TIGR underscores the importance of basic science and curiosity-driven research. Just as CRISPR emerged from studying bacterial immune systems, TIGR may unlock new possibilities by revealing nature's hidden molecular tools.
CRISPR has transformed biotechnology and medicine by enabling precise gene editing, offering hope for curing genetic diseases. Feng Zhang's pioneering work laid the foundation for this revolution. Now, his exploration of TIGR promises to push the boundaries even further, potentially overcoming CRISPR's limitations and opening new horizons in gene therapy and synthetic biology. The story of TIGR is a testament to the power of curiosity and the endless potential of understanding life at its most fundamental level.
