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Successor to Crispr - The SciShow channel

4 min read

https://www.youtube.com/watch?v=_UimlaolxiA

SciShow Field Trip: Feng Zhang and the Future of Gene Editing

This summary covers the SciShow Field Trip episode featuring Dr. Feng Zhang at the Broad Institute, exploring the evolution of CRISPR and the discovery of a new, potentially superior gene-editing tool called TIGR-Tas.

🧬 The Revolution of CRISPR

CRISPR is described as one of the most significant biotech game-changers in history. In just over a decade, it evolved from a theoretical bacterial defense mechanism to a tool capable of rewriting the DNA of a living infant to cure a genetic disorder.

How it Works

  • Origin: It is an immune system found in bacteria to defend against viruses.
  • Mechanism: A snippet of RNA acts as a tour guide to match a specific DNA sequence, and a Cas protein (like Cas9) acts as scissors to cut that section out.
  • Zhang’s Contribution: While Emmanuelle Charpentier and Jennifer Doudna (Nobel Prize winners) discovered how CRISPR works, Feng Zhang was the first to adapt it for use in eukaryotic cells (mice and humans).

Evolution of the Tool

Zhang’s lab continued to refine the system, discovering Cas12a, which is:

  • Smaller than Cas9.
  • Easier to get into cells.
  • Makes a “jagged” cut rather than a blunt one, which is better for gene editing as it reduces unwanted mutations.

👨‍🔬 Spotlight: Dr. Feng Zhang

Dr. Zhang is a pioneer in the field who approaches biology with an engineer’s mindset.

  • Background: The child of computer scientists, he realized in 7th grade that biology is essentially “code.” If you change the code (DNA), you change the output (cell behavior).
  • Philosophy: He is a proponent of Basic Science—researching fundamental principles without immediately worrying about a commercial application. He believes unexpected results in basic research lead to the biggest breakthroughs.
  • Early Work: He started by studying Green Fluorescent Protein (GFP) to track how viruses infect cells.

🐯 The New Frontier: TIGR-Tas

While CRISPR is powerful, it has limitations, particularly regarding delivery into the body and treating complex diseases. Zhang has returned to the lab to study a new system called TIGR-Tas.

What is TIGR?

  • Acronym: Tandem Interspaced Guide RNA.
  • Source: Unlike CRISPR (mostly bacterial), TIGR is found primarily in viruses. It is likely a system viruses use to insert their genetic material into bacteria.

Advantages over CRISPR

  1. Higher Accuracy: TIGR reads both sides of the DNA double helix before cutting, potentially reducing errors.
  2. Smaller Size: Because it is more compact, it is easier to deliver into difficult-to-reach tissues.
  3. Better Precision: It does not require as wide a “targeting window” as CRISPR, allowing for more specific edits.

Potential Applications

Because TIGR is smaller and easier to deliver, it holds promise for treating diseases of the nervous system (such as ALS, Huntington’s, Alzheimer’s, or Parkinson’s), where delivering bulky CRISPR machinery into brain cells is currently difficult.

🧪 The Scientific Process

The video highlights the labor-intensive process of “reverse engineering life”:

  1. Identification: Finding the gene sequences in nature (bacteria/viruses).
  2. Synthesis: Ordering the specific DNA code online (often costing only ~$20).
  3. Testing: Transplanting the code into E. coli, purifying the protein, and testing it in human cells in petri dishes.
  4. Vector Creation: Using high-speed centrifuges (spinning at 100,000x gravity) to create viral vectors to deliver the gene therapy.

🏁 Conclusion

While CRISPR has already begun to cure diseases like sickle cell anemia, the discovery of TIGR-Tas suggests we are only at the beginning of the gene-editing revolution. By studying the ancient evolutionary arms race between bacteria and viruses, scientists like Feng Zhang are developing the tools to treat previously incurable human conditions.

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