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L01 — The Molecular Scissors

Module: M06 — Rewriting Life
Periods: 1
NGSS: HS-LS1-1
Lesson Type: Launch / Explore

Learning Objective

  • By the end of this lesson, students will be able to explain how CRISPR-Cas9 finds and cuts a specific DNA sequence by modeling the guide RNA, target DNA, and Cas9 protein interaction.

Phenomenon / Hook

Show a 2-minute clip of Victoria Gray — the first person cured of sickle cell disease using CRISPR. Video: Can CRISPR cure Sickle-cell Disease? (Nature Video, 2021 — show 0:00–2:30) Pose the question: “Scientists edited her DNA to fix a disease. How is it possible to find one mistake among 3 billion letters of genetic code — and fix it?”

Materials

  • Projector / YouTube: Can CRISPR cure Sickle-cell Disease? (Nature Video, 2021)
  • Paper strip “DNA” models (pre-cut, one per student pair)
  • “Guide RNA” sticky strips (colored differently)
  • Scissors (representing Cas9)
  • Handout: [[resources/handouts/crispr-mechanism-diagram]]
  • Diagram: [[resources/images/crispr-mechanism-diagram.png]]

Agenda

Opening (8 min)

  • Show Victoria Gray phenomenon (2 min video or image + 1-sentence read-aloud)
  • Think-Pair-Share: “What does it mean to ‘edit’ DNA? What tools might you need?” (3 min)
  • Share out, collect guesses on board (3 min)

Explore (15 min)

  • Paper Model Activity: Students work in pairs
    • Each pair gets a paper DNA strand (~200 “bases”) with a highlighted target sequence
    • They attach a “guide RNA” strip (must be complementary to the target)
    • They simulate Cas9 cutting at the correct location with scissors
    • Guiding questions on handout:
      1. What must the guide RNA match to find the right spot?
      2. Why does Cas9 need BOTH the guide RNA AND the target DNA?
      3. What happens to the DNA after the cut?

Explain (10 min)

  • Teacher-led mini-lesson: CRISPR-Cas9 mechanism
    • Guide RNA = GPS coordinates
    • Cas9 = molecular scissors
    • PAM sequence = “license plate” that Cas9 checks before cutting
    • After the cut: cell’s own repair machinery fixes the break (NHEJ or HDR)
  • Students annotate their handout with key vocabulary

Elaborate (7 min)

  • Quick write: “How is CRISPR different from the gene editing that has always happened naturally through mutations?”
  • Emphasize: CRISPR is targeted — nature’s mutations are random

Closing (5 min)

  • Exit Ticket: [[exit-tickets/L01-exit-ticket]]
    1. What are the two components of the CRISPR-Cas9 system? What does each do?
    2. Why can’t Cas9 cut DNA without a guide RNA?

Differentiation

SupportExtension
Pre-label the target sequence on the paper DNA so struggling students can focus on the mechanismAsk students to research the origin of CRISPR — it’s a bacterial immune system. Why would bacteria need gene editing?
Provide a word bank: guide RNA, Cas9, complementary, target sequence, PAMStudents predict: what would happen if the guide RNA matched multiple sequences? (off-target effects)

Assessment

  • Formative: Circulate during paper model activity; check for accurate pairing of guide RNA to target
  • Exit Ticket: Two recall/application questions

Teacher Notes

  • Cut paper strips in advance — this saves 5+ minutes.
  • The PAM sequence is a nuance; don’t overcomplicate. Mention it, but the core takeaway is guide RNA + Cas9 = targeted cut.
  • If students ask “where did CRISPR come from?”, briefly note it’s a bacterial defense against viruses. Save the full story for a curiosity extension.