Module 18 · 70 min

Translational Frontier: Cell & Gene Therapy

What cell biology has put in clinic — and what it has promised but not yet delivered.

CoreClinicalResearch

Topics

What this module covers

01AAV gene therapy: Luxturna, Zolgensma, Hemgenix
02Lentiviral ex vivo therapy: Skysona, Zynteglo
03CRISPR therapeutics: Casgevy in vivo and ex vivo
04Allogeneic 'off-the-shelf' CAR-T and CAR-NK
05Tumour-infiltrating lymphocyte therapy (lifileucel)
06Senolytics, ferroptosis-modulators, mitochondrial transplant — frontier hype filter

Deep dives

Lesson sub-pages

research 27 min· 3 refs

In vivo CRISPR and base editing: from idea to approved therapy

Casgevy, in vivo PCSK9 editing, and what the next decade of one-shot genetic medicine looks like.

Learning objectives

By the end of this module you will be able to

L01List approved cell/gene therapies, indications, and modality.
L02Explain immunogenicity considerations for AAV (capsid serology, redosing).
L03Critically evaluate a 'breakthrough' headline using evidence-grade reasoning.

Expected takeaways

What you should walk away believing

→Gene/cell therapies are real and curative for selected monogenic and oncologic indications, but expensive, manufacturing-bound, and not without risk.
→Senolytics and partial-reprogramming claims are exciting but largely preclinical in humans.
→Always compare a 'cure' headline to baseline natural history and the comparator arm.

Core summary

At the Core level

Cell biology has now produced therapies that durably correct genetic disease. But every approval comes with limits: Zolgensma's window of efficacy, Casgevy's myeloablation cost, CAR-T's CRS risk, and cost structures that strain even rich health systems. The next wave — in vivo editing, off-the-shelf cell therapy, organ regeneration — is plausible but unfinished.

Evidence-graded claims

Claims, scored A–F

Onasemnogene abeparvovec is curative for SMA type 1 if given pre-symptomatically

Strong durable benefit; very long-term follow-up incomplete.

Senolytic combinations (D + Q) extend human lifespan

Encouraging early-phase data; lifespan claims premature.

Mitochondrial transplant treats heart failure

Single-centre paediatric ECMO data; not standard of care.

Quiz

Check your understanding

Q1. AAV redosing is limited primarily by:

Q2. Lifileucel is:

Flashcards

Lock it in

1 / 3

Front

Casgevy mechanism?

Click to flip

Primary literature

Gene therapy comes of age — Dunbar et al., Science 2018 ↗
Tumor-infiltrating lymphocyte therapy for advanced melanoma (lifileucel) — Chesney et al., J Immunother Cancer 2022 ↗

Methods: Microscopy, Omics & Genome Editing