4 episodes
The Translational Mixer Andy Marshall
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- Science
Two lapsed Nature editors, Andy Marshall and Juan-Carlos Lopez, have a conversation and a cocktail with experts in translational research and biomedicine
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Episode 4: Dan Kaufman on off-the-shelf cell therapy and Manhattans
UCSD's Dan Kaufman, an innovator in the field of induced pluripotent cell (iPSC)-derived natural killer cell therapies, talks to Andy and JC about the latest in allogeneic and autologous immune and regenerative cell therapies at the 2024 Keystone symposium on Emerging Cell Therapies.
02:55 Sourcing and expanding NK cells
05:59 Off-the-shelf versus self
09:26. Clinical trials and manufacturing
13:40. Stealth, immune cloaking and protein manufacture
16:51. Safety, cost, availability and standardization
22:00. Stampede into autoimmune disease
28:59. Neurological cell therapies and beyond
33:30. Off the shelf and in vivo engineering
38:13. Commercialization headaches
39:51. Dan’s drink
The Manhattan:
2 Oz rye whiskey,
1 Oz sweet vermouth,
2 dashes aromatic bitters.
DIRECTIONS: Stir on ice for 45 sec and strain over a coupe glass. Garnish with a maraschino cherry.
The Mixer music “Pour Me Another” courtesy of Smooth Moves! -
Episode 3: Kiran Musunuru, gene and base editors hit the clinic and a Bloody Mary mix
UPenn's Kiran Musunuru, a human geneticist and practicing cardiologist who has pioneered the translation of gene- and base-editing approaches, talks to JC and Andy about the latest clinical results and modalities discussed at the 2024 Keystone symposium on Precision Genome Engineering.
4:07 Impacting patients
6:44 In vivo editing in different liver diseases
11:37 The FDA stance on programmable therapy
19:41 Base-editors march into the clinic
25:54 Multiplexing with base editors
28:57 Reaching broader patient populations
33:32 Investigator-initiated trials
39:27 Prime and epigenetic editing
44:34 Excitement around Bridge RNAs
47:15 Kiran’s mocktail
Bloody Mary 3 Ways
4oz (120 ml) tomato juice
1/2oz (15 ml) fresh lemon juice
1/4oz (7 ml) Worcestershire sauce
1/2 barspoon (3 ml) prepared horseradish, or to taste
2 dashes Tabasco, or to taste
Celery stick, for garnish
Salt and freshly ground pepper
Your choice of pickled vegetables, skewered on a cocktail pick, for garnish
DIRECTIONS: Add the tomato juice, lemon juice, Worcestershire, horseradish, and Tabasco to a shaker tin with ice and gently shake for 5 seconds. Strain into a chilled double rocks glass over a large ice cube. Garnish with the celery stick, salt, pepper, and pickled vegetables and serve.
For alcoholophiles, add 2oz (60 ml) vodka to the tomato juice, lemon, Worcestershire, horseradish and Tabasco. Enjoy!
Refs:
Gilmore et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med 385, 493-502 (2021) DOI: 10.1056/NEJMoa2107454
Chiesa et al . Base-edited CAR7 T cells for relapsed T-cell acute lymphoblastic leukemia. N Engl J Med 389, 899-910 (2023) DOI: 10.1056/NEJMoa2300709
Longhurst et al. CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema N Engl J Med 390, 432-441 (2024) DOI: 10.1056/NEJMoa2309149
Durrant et al. Bridge RNAs direct modular and programmable recombination of target and donor DNA. https://www.biorxiv.org/content/10.1101/2024.01.24.577089v1
Keystone Meeting on Precision Genome Engineering
Somatic Cell Genome Editing Consortium
The Mixer music “Pour Me Another” courtesy of Smooth Moves! -
Episode 2: Eric Topol, multimodal AI models in medicine, and a glass of Merlot
Scripps' Eric Topol is a visionary in the application of artificial intelligence to medicine. He has a wide-ranging conversation with JC and Andy about :
02:52 Multimodal AI is coming
06:44 FDA-approved AI software
10:02 How to validate AI models?
12:50 Synthetic doctor’s notes and other early applications
15:38 Thinking about the model and its training
19:28 Dealing with hallucination and GPT5
24:13 Low-to-middle income countries
27:40 Uptake by the medical community
29:15 Open or proprietary?
35:46 What to do with the data?
39:46 Eric’s elixir
1) His September 2023 Science editorial,
2) Derma Sensor.
3) Wowser package AMIE (Articulate Medical Intelligence Explorer) a descendant of MedPalm 2
4) A recent Science essay on diagnoses.
Eric’s Elixir:
Pinot Noir!
Marimar Mas Cavalls Pinot Noir 2018 from Russian River Valley, CA, USA.
Cristom Marjorie Vineyard Pinot Noir 2021 from Villamette Valley, OR, USA
Racines Pinot Noir Santa Rita Hills 2017 from Santa Rita Hills, CA, USA
The Mixer music “Pour Me Another” courtesy of Smooth Moves! -
Episode 1: Pete Kirkpatrick, mRNA therapeutics and Espresso Martinis
Pete Kirkpatrick, Chief Editor of Nature Reviews Drug Discovery, gives Andy and JC the lowdown on a Nature Conference on RNA therapeutics and what innovations he is seeing in the field of mRNA therapies.
01:44 Nature conference on RNA therapies
08:11 Differences between mRNA therapeutics and mRNA vaccines
14:24 mRNA chemistries
18:08 mRNA manufacturing
22:05 mRNA delivery
27:21 Delivering LNPs to organs other than liver
34:25 Targeting RNA with small molecules
39:35 RNA-guided CRISPR, base and prime editing therapies
48:35 Pete’s tipple
Pete's tipple of choice:
Expresso Martini
1.5 Oz vodka, 1 Oz coffee liqueur, 1.5 Oz espresso.
Shake over large ice cubes for 10-12 sec and strain into a Martini glass.
Garnish with roasted coffee beans.
(N.B. Ideally, 1.5 Oz of espresso should come from ~20 g of ground coffee.)
The Mixer music “Pour Me Another” courtesy of Smooth Moves!