Skip to content
ContentLora

    Tip: press / anywhere to search.

    Explainer

    How CRISPR gene editing works: cutting, base and prime editing

    CRISPR-Cas9 is a bacterial immune tool that a guide RNA can point at a chosen DNA sequence so it cuts there.[1][2] Newer base and prime editors build on Cas9 to rewrite DNA letters without cutting both strands.[3][4]

    Editor reviewedStrict sourcingUpdated Gene editing and gene therapyLife sciencesHealth and medicine

    Gene editing changes the DNA sequence inside living cells.[5] Today’s tools grew out of one discovery: a bacterial enzyme that can be programmed to find a chosen stretch of DNA.[2]

    The CRISPR-Cas9 system

    CRISPR-Cas9 started out as part of an immune system that bacteria use.[1] In 2012, researchers showed that the Cas9 protein can be steered by a short piece of RNA to cut DNA at a matching spot. They also suggested it could be reprogrammed to edit genes.[2]

    Think of the guide RNA as a search term and Cas9 as the scissors. Genome editing tools act like scissors that cut DNA at a specific spot.[5] CRISPR made this much easier. NHGRI describes it as simpler, faster, cheaper and more accurate than older methods.[6] Two of the scientists behind the 2012 work shared the 2020 Nobel Prize in Chemistry.[7]

    In the native system, a CRISPR RNA base-paired with a trans-activating CRISPR RNA forms a dual-RNA structure. That structure directs Cas9 to make a double-strand break at a complementary DNA site. Jinek and colleagues proposed exploiting this for RNA-programmable genome editing.[2] Nuclease-based therapies use such breaks to disrupt a target. Casgevy, for example, disrupts the BCL11A erythroid enhancer to raise fetal hemoglobin.[8] In vivo programs such as lonvo-z inactivate the KLKB1 gene.[9]

    Base editing: changing one letter

    Cutting both strands of DNA is a blunt way to fix a one-letter typo. Base editors, first described in 2016, change one DNA letter into another without cutting through the double helix.[3] In the original experiments, unwanted insertions or deletions were typically 1% or fewer.[3]

    The 2016 Nature paper reported programmable, irreversible base conversion without double-strand DNA backbone cleavage, with typically ≤1% indels.[3] In clinical use, a personalized base editor delivered by lipid nanoparticles treated an infant with CPS1 deficiency in 2025.[10] BEAM-302 is in a pivotal cohort for alpha-1 antitrypsin deficiency as of 2026.[11]

    Prime editing: search and replace

    Prime editing, described in 2019, carries its own template for the new DNA text. It can insert or delete short pieces and make any single-letter change, again without a double-strand break.[4] Its developers estimated it could in principle correct up to 89% of known disease-causing variants.[12]

    A prime editor combines a catalytically impaired Cas9 with an engineered reverse transcriptase. A prime editing guide RNA (pegRNA) both specifies the target and encodes the edit. The original paper demonstrated targeted insertions, deletions and all 12 point-mutation types without donor DNA.[4] The first human data came in 2025 from an ex vivo prime-edited stem cell therapy for chronic granulomatous disease.[13]

    Somatic versus germline editing

    The therapies in this course edit somatic (body) cells, so their effects stay with the patient. Editing eggs, sperm or embryos would change the germline and be inherited.[14] NHGRI says most people agree germline cells should not be edited at this time.[15] In 2021 WHO issued governance recommendations for human genome editing, including a mechanism for reporting unethical research.[16]

    Getting the editor into cells

    An editor is only useful if it reaches the right cells. Cells can be edited outside the body and returned, or the editor can be delivered into the body.[17] The next page in the course explains these delivery methods.

    Questions readers ask

    Where does CRISPR come from?

    From bacteria. CRISPR-Cas9 is part of an adaptive immune system in bacteria that researchers repurposed as a programmable DNA-cutting tool.[1]

    How does Cas9 know where to cut?

    A guide made of RNA pairs with the target DNA sequence and directs Cas9 to make a double-stranded break there. Changing the guide changes the target.[2]

    Why were base and prime editors invented?

    To change DNA more precisely. Base editors convert one base into another without cutting both strands, and prime editors write small insertions, deletions or any single-base change from an RNA template.[3][4]

    Do CRISPR edits get passed to children?

    Only if reproductive (germline) cells are edited. Edits to body (somatic) cells affect only the treated person, and current therapies edit somatic cells.[14]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      CRISPR-Cas9 comes from an adaptive immune system that bacteria use, which researchers repurposed as a programmable DNA-cutting tool. confirmedas of 2026-10-10

    2. [2]

      A 2012 Science paper by Jinek, Doudna, Charpentier and colleagues showed that a two-RNA structure directs the Cas9 protein to make double-stranded breaks in target DNA, and highlighted its potential for RNA-programmable genome editing. confirmedas of 2026-10-10

    3. [3]

      Base editing, reported in Nature in 2016, converts one DNA base into another in a programmable way without cutting both DNA strands, with typically 1% or fewer unwanted insertions or deletions in the original experiments. confirmedas of 2026-10-10

    4. [4]

      Prime editing, reported in Nature in 2019, pairs an impaired Cas9 with an engineered reverse transcriptase and a prime editing guide RNA (pegRNA) that both finds the target and encodes the edit, allowing insertions, deletions and all 12 kinds of single-base change without double-strand breaks or donor DNA. confirmedas of 2026-10-10

    5. [5]

      Genome editing is a set of methods for changing the DNA of organisms; the tools act like scissors that cut DNA at a chosen spot. confirmedas of 2026-10-10

    6. [6]

      The US National Human Genome Research Institute describes CRISPR as simpler, faster, cheaper and more accurate than older genome-editing methods. confirmedas of 2026-10-10

    7. [7]

      Jennifer Doudna and Emmanuelle Charpentier shared the 2020 Nobel Prize in Chemistry for developing CRISPR-Cas9 genome editing. confirmedas of 2026-10-10

    8. [8]

      Casgevy's approach edits a patient's blood stem cells outside the body by electroporating them with CRISPR-Cas9 aimed at an enhancer of the BCL11A gene, a gene that represses fetal hemoglobin, so that the cells make more fetal hemoglobin. confirmedas of 2026-10-10

    9. [9]

      Lonvo-z (lonvoguran ziclumeran) is Intellia's one-time, in vivo CRISPR/Cas9 treatment for hereditary angioedema, designed to permanently lower kallikrein by inactivating the KLKB1 gene, and given in an outpatient setting. confirmedas of 2026-10-10

    10. [10]

      In 2025 a team at Children's Hospital of Philadelphia and Penn Medicine designed and manufactured, within about six months, a personalized base-editing therapy delivered by lipid nanoparticles to the liver for an infant with severe CPS1 deficiency, a rare urea-cycle disorder. confirmedas of 2026-10-10

    11. [11]

      In July 2026 Beam dosed the first patient in the global pivotal cohort of its BEAM-302 trial in AATD-associated lung disease. confirmedas of 2026-10-10

    12. [12]

      The 2019 prime editing paper estimated that the method could in principle correct up to 89% of known disease-associated genetic variants. confirmedas of 2026-10-10

    13. [13]

      In May 2025 Prime Medicine reported the first clinical data for prime editing in humans, from PM359, an ex vivo prime-edited stem cell therapy for chronic granulomatous disease (CGD); the first patient reached 58% DHR-positive neutrophils by day 15 and 66% by day 30, with no serious adverse events related to PM359. confirmedas of 2026-10-10

    14. [14]

      Edits to somatic (body) cells affect only the person treated, while edits to germline (reproductive) cells are passed on to future generations. confirmedas of 2026-10-10

    15. [15]

      NHGRI states that most people agree germline cells should not be edited at this time, and that NIH does not fund research to edit human embryos. confirmedas of 2026-10-10

    16. [16]

      In July 2021 the World Health Organization issued its first global recommendations on governing human genome editing, including steps toward a trial registry and a confidential channel for reporting unethical or illegal research. confirmedas of 2026-10-10

    17. [17]

      Early CRISPR therapies edited cells outside the body (ex vivo); newer approaches deliver the editor into the patient (in vivo), which a 2025 review notes faces lower delivery efficiency, off-target effects and instability. confirmedas of 2026-10-10

    Revision history (1)
    1. Page created.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "How CRISPR gene editing works: cutting, base and prime editing." ContentLora, updated Oct 10, 2026. https://contentlora.com/explain/how-crispr-works

    Spotted an error? Suggest a correction or emailcorrections@contentlora.com.

    Keep exploring

    ☰ Contents