# Genetic Engineering / Beyond CRISPR Canonical URL: https://shipslides.com/d/catalog-future-genetic-engineering Raw viewer URL: https://content.shipslides.com/d/catalog-future-genetic-engineering/raw Category: Future Slides: 13 Updated: 2026-05-17T20:55:58.672Z Tags: catalog, future, genetic, engineering ## Summary From cutting DNA to rewriting it. A field-tour of base editors, prime editors, epigenetic switches, gene drives, and the engineered organisms that will define the next decade of biology. Key sections include: GENETIC ENGINEERING Beyond CRISPR; CRISPR-Cas9, 2012; Base editing — change one letter, never break the strand; Prime editing, 2019; Epigenetic editing — turn genes on or off, no scissors; Delivery is the bottleneck; Approved therapies, today; Heritable editing — He Jiankui, 2018; Gene drives — edits that copy themselves; Xenotransplantation, edited. ## Slide Outline 1. GENETIC ENGINEERING Beyond CRISPR 2. CRISPR-Cas9, 2012 3. Base editing — change one letter, never break the strand 4. Prime editing, 2019 5. Epigenetic editing — turn genes on or off, no scissors 6. Delivery is the bottleneck 7. Approved therapies, today 8. Heritable editing — He Jiankui, 2018 9. Gene drives — edits that copy themselves 10. Xenotransplantation, edited 11. De-extinction 12. The honest assessment 13. References & further viewing ## Slide Transcript ### Slide 1: GENETIC ENGINEERING Beyond CRISPR - A 13-Slide Briefing · 2026 - From cutting DNA to rewriting it. A field-tour of base editors, prime editors, epigenetic switches, gene drives, and the engineered organisms that will define the next decade of biology. - K. Ning - · - Catalog Series - · - 13 Slides ### Slide 2: CRISPR-Cas9, 2012 - Slide 02 · The Base Layer - A bacterial immune system, repurposed by Doudna and Charpentier into a programmable molecular scalpel. Give it a 20-letter RNA guide and it cuts that exact spot in any genome — bacteria, plant, mouse, human. - Programmable: swap the guide RNA, change the target. - Cheap: reagents cost a graduate student less than lunch. - Blunt: double-strand breaks heal messily; the cell improvises. - Foundational: every editor on the next slides is built on Cas9. ### Slide 3: Base editing — change one letter, never break the strand - Slide 03 · Single-Letter Surgery - David Liu's lab, 2016. Take a deactivated Cas9 (it can find but not cut), bolt on a deaminase enzyme, and you can flip a single C to T or A to G. Most known disease mutations are point mutations — this addresses them directly. - CBE - Cytosine Base Editor - Converts C·G to T·A. The first base editor; useful for installing stop codons or disrupting splice sites. - ABE - Adenine Base Editor - Converts A·T to G·C. Engineered from a tRNA deaminase — nature didn't have a DNA version, so the lab built one. - Why it matters - No double-strand breaks - Far fewer indels, translocations, large deletions. The cell's repair machinery never gets to improvise. - Verve Therapeutics, 2022: first in-human base editing trial. One injection, lifelong cholesterol reduction by editing PCSK9 in liver cells. ### Slide 4: Prime editing, 2019 - Slide 04 · Search and Replace - Liu lab again. Cas9 nickase (cuts only one strand) fused to a reverse transcriptase, guided by an extended pegRNA that encodes the new sequence. The cell rewrites itself to match the template. - Can install any single-letter swap, plus small insertions and deletions. - Estimated to address ~89% of known pathogenic human variants. - Twin Prime, PASTE, and other variants now insert whole genes. - First clinical trials began 2024 (Prime Medicine, chronic granulomatous disease). - BEFORE - 5'... A T G C A G T A C ...3' - 3'... T A C G T C A T G ...5' - ↓ pegRNA template - AFTER - 5'... A T G G G T T A C ...3' - 3'... T A C C C A A T G ...5' - A precise three-letter substitution — no double-strand break, no donor template required. ### Slide 5: Epigenetic editing — turn genes on or off, no scissors - Slide 05 · The Volume Knob - Fuse dead Cas9 to a transcription activator (VPR), repressor (KRAB), or methyltransferase (DNMT3A). The DNA sequence is preserved; only the chemical marks around it change. The cell keeps the new setting through divisions. - CRISPRa activate - dCas9-VPR recruits the transcription machinery; turn a gene up 10x to 1000x without touching its sequence. - CRISPRi interfere - dCas9-KRAB blocks transcription — reversibly silence a gene. Tunable, and you can switch it back. - CRISPRoff durable - A 2021 fusion that writes methyl marks — one transient hit, silencing that propagates through cell divisions. - The pitch: for many diseases (pain, cardiovascular risk, addiction) you don't want to permanently rewrite the genome — you want to dial the volume. Tune Therapeutics is in trials silencing PCSK9 and Hep B this way. ### Slide 6: Delivery is the bottleneck - Slide 06 · The Hard Part - Editing the genome in a dish is now routine. Editing it inside a living person, in the right tissue, without breaking everything else — that is the actual frontier. - Lipid nanoparticles (LNPs): the mRNA-vaccine envelope. Goes naturally to liver. One dose, transient editor expression. - AAV vectors: stripped-down viruses. Tissue-specific tropism, but small payload (~4.7 kb) and pre-existing immunity. - Electroporation: for ex vivo — pull cells out, zap them, put them back. The Casgevy approach. - Engineered virus-like particles: deliver protein-RNA complexes directly, no DNA cargo. - Where edits go today - Liver - Eye - Muscle - CNS - Lung - Kidney - Approximate clinical viability of in vivo delivery, 2025. Liver is solved. Most other tissues are not. ### Slide 7: Approved therapies, today - Slide 07 · In the Clinic - For most of the 2010s, gene therapy was a promise. By 2025 it is a billing code. Three landmarks: - 2023 · FDA & MHRA - Casgevy - Vertex / CRISPR Therapeutics - First CRISPR therapy ever approved. Edits patient's own stem cells ex vivo to reactivate fetal hemoglobin. Cures sickle cell disease and beta-thalassemia. ~$2.2M per patient. - 2017 · FDA - Luxturna - Spark Therapeutics - First FDA-approved gene therapy for an inherited disease. Subretinal AAV2 injection delivers a working copy of RPE65 — restores vision in a form of Leber congenital amaurosis. - 2019 · FDA - Zolgensma - Novartis - One-time IV infusion for spinal muscular atrophy in infants. Delivers a working SMN1 via AAV9. $2.1M list price — for years the most expensive drug in history. - ~20 - Approved gene/cell therapies (US, 2025) - ~3,000 - Active clinical trials worldwide - 7,000+ - Known monogenic diseases — potential targets - $1-3M - Typical price tag — the next bottleneck ### Slide 8: Heritable editing — He Jiankui, 2018 - Slide 08 · The Line That Was Crossed - A Chinese researcher announced he had edited CCR5 in human embryos and brought twin girls (and later a third child) to term. Aim: HIV resistance. Outcome: global condemnation, three years in prison, an indefinite scientific moratorium. - The edits were imprecise — not the published natural variant; novel mutations whose effects are unknown. - Changes affect every cell, including sperm and eggs — passed to descendants forever. - WHO, NAS, and the UK Royal Society called for a global moratorium on clinical germline editing. - The technical barrier is gone. The barrier now is governance, consent, and political will. - Why this stays hard - Mosaicism. Editing reaches different cells at different rates — an embryo can carry multiple genotypes. - Off-targets. A mistake in the germline propagates through every future generation. - Pleiotropy. A "disease" gene often does many things. CCR5 disruption may raise West Nile risk. - Consent. The edited person never agreed; neither did their descendants. - For now: PGT (embryo selection) handles most heritable disease ethically. Germline editing's case is narrow. ### Slide 9: Gene drives — edits that copy themselves - Slide 09 · CRISPR For Ecosystems - Normal inheritance: a trait passes to ~50% of offspring. A gene drive carries the editing machinery itself, so it converts the second chromosome too — spreading to ~100% of offspring, generation after generation, until the trait saturates a population. - The dilemma: a successful drive could end malaria (600,000 deaths/year). It could also unintentionally drive a species extinct, or jump to a non-target species. Daisy-chain and split drives are designed to self-limit — but no one has yet released one in the wild. ### Slide 10: Xenotransplantation, edited - Slide 10 · Pigs As Organ Donors - ~17 people die every day in the US waiting for a transplant. eGenesis and Revivicor have engineered pigs with dozens of CRISPR edits — knocking out the antigens that trigger human rejection, inactivating endogenous pig retroviruses, adding human immune-regulator genes. - Sept 2021: NYU surgeons attach an edited pig kidney to a brain-dead recipient — it functions for 54 hours. - Jan 2022: University of Maryland transplants a 10-edit pig heart into David Bennett. Survives 60 days. - Mar 2024: Mass General performs the first edited pig kidney into a living patient. Survives ~2 months. - 2025: First formal Phase 1 clinical trials begin (United Therapeutics, eGenesis). - CRISPR edits in eGenesis donor pigs - pig glycan antigens knocked out (alpha-Gal, Neu5Gc, Sda) - PERV (porcine retrovirus) sites inactivated - human transgenes added (CD46, CD55, thrombomodulin, …) - ~100k - people on US transplant waitlist ### Slide 11: De-extinction - Slide 11 · Reverse Gear - Colossal Biosciences (and others) are trying to bring back lost species — not by cloning ancient DNA (it's too degraded) but by editing the closest living relative's genome to express extinct traits. - Woolly Mammoth - Target: 2028 - Edit Asian elephant cells with mammoth-derived alleles for cold tolerance, hair, fat. In 2024 Colossal announced elephant-derived iPSCs — a major prerequisite. Many edits still ahead. - Thylacine - Tasmanian tiger - Closest living relative is the fat-tailed dunnart, a mouse-sized marsupial. The genome gap is enormous. Colossal sequenced a 110-year-old specimen in 2024. - Dodo - Extinct ~1681 - Edit Nicobar pigeon (closest relative) cells. In 2025 Colossal achieved primordial germ cell culture in pigeons — the bird-genetics equivalent of iPSCs. - The honest framing: what's actually being made is an elephant with mammoth-like traits, not a mammoth. The technology spinning out (large-scale editing, exotic IVF, cell reprogramming) may matter more than any resurrected animal — particularly for endangered-species rescue. ### Slide 12: The honest assessment - Slide 12 · Where We Actually Are - Real and growing - Somatic editing for monogenic disease: working, approved, scaling. - Liver-targeted in vivo editing: a platform with dozens of programs. - Engineered T-cells for cancer: a new pillar of oncology. - Pig organs in human bodies: now a clinical reality, not a thought experiment. - Crops with bespoke traits: deregulated edits in wheat, tomato, soy. - Fraught and unresolved - Heritable editing: technically near, ethically and politically nowhere near consensus. - Gene drives: reversibility uncertain; first wild release will set precedent for all biology. - Polygenic enhancement: marketing outpaces science; modest selection effects only. - Cost and access: $2M therapies don't scale to global disease burden as built. - Off-targets: the long tail of "we won't know for 30 years." - The next decade is less about new editors and more about delivery, durability, and decisions — technical, regulatory, and moral. ### Slide 13: References & further viewing - Slide 13 · Going Deeper - Reading - Doudna & Sternberg, A Crack in Creation (2017) - Walter Isaacson, The Code Breaker (2021) - Kevin Davies, Editing Humanity (2020) - Liu lab papers: Nature 2017 (ABE), Nature 2019 (prime editing) - Innovative Genomics Institute — innovativegenomics.org - Broad Institute editing primer — broadinstitute.org - Watch - YOUTUBE · SEARCH - CRISPR gene editing — the future - Talks from Doudna, Liu, Zhang; documentary primers - YOUTUBE · SEARCH - He Jiankui — the CRISPR babies - News reporting, ethics panels, interviews after release - GENETIC ENGINEERING / Beyond CRISPR - Catalog Series · 2026 - End of deck — press ← to revisit. ## Related Decks - [Genetic Engineering](https://shipslides.com/d/future-genetic-engineering) - [AGI // The Most Consequential Question](https://shipslides.com/d/catalog-future-agi) - [BCI // Reading and Writing to the Brain](https://shipslides.com/d/catalog-future-bci) - [CLIMATE / 2026 - 2100](https://shipslides.com/d/catalog-future-climate)