Reprogrammed: A biotechnology Podcast

Jack Treml

Reprogrammed in a biotechnology podcast that explores a new topic every season through examining a series of seminal papers. This podcast supports a Selected Topics in Biotechnology course at the University of Kansas' Edwards Campus - but you don't need to be in that course to listen!

  1. S2Ep10: Interview with Dr. Maria Deza Leon

    15 de mai.

    S2Ep10: Interview with Dr. Maria Deza Leon

    This interview followed a Keynote speech Dr. Deza Leon gave at the 2026 Hawk Talks Event at KU Edwards Campus on May 1.

    42 min
  2. S2Ep9: What’s in the Box: the making of a damn fine vaccine

    13 de abr.

    S2Ep9: What’s in the Box: the making of a damn fine vaccine

    This episode looks at two papers, one a 2019 paper by Hassett et al. about optimizing Lipid Nanoparticles specifically for intramuscular mRNA vaccines. And a second, Laczko et al., from 2020, that shows what kind of immune responses you can get from nucleoside-modified mRNA-LNP after a single shot in mice. Together, these explain why mRNA vaccines aren’t just ‘RNA magic.’ They’re a delivery story, and an immune-programming story.

    21 min
  3. S2Ep7: Something looks off here

    29 de mar.

    S2Ep7: Something looks off here

    This episode discusses the 2005 Kariko et al. paper about RNA immunogenicity.

    21 min
  4. S2Ep6: How to Outpace a Killer Virus

    9 de mar.

    S2Ep6: How to Outpace a Killer Virus

    In this episode, we explain why influenza is such a persistent threat—its segmented RNA genome enables antigenic drift and reassortment-driven “shift,” letting it change faster than traditional vaccines can be manufactured. We thenwalk through Petsch et al. (2012), showing that synthetic mRNA vaccines elicit functional anti-HA antibodies measured by HAI, protect mice from lethal influenza challenge (with protection transferable by antibody), and cangenerate remarkably durable immunity—highlighting the real breakthrough: turning vaccine development from slow biological manufacturing into speed-of-information medicine.

    19 min
  5. S2Ep5: The call is coming from inside the house

    5 de mar.

    S2Ep5: The call is coming from inside the house

    mRNA vaccines: when the call is coming from inside the house, discusses how the immune system knows what's going on inside of cells and how specific that knowledge is. This episode explains MHC Haplotype and how MHC restriction limits the targets of CTLs.

    26 min
  6. Show me the CTLs

    26 de fev.

    Show me the CTLs

    This episode explores an early mRNA vaccination study showing that injected RNA can be injected into the body, be translated into protein that is presented on MHC class I to generate an antigen-specific cytotoxic T-cell respons. This discussion highlights how researchers moved from simply proving in-vivo protein expression to demonstrating that nucleic acids themselves could function as immunogens—laying the conceptual groundwork for modern mRNA vaccines.

    23 min

  7. 17 de fev.

    Programmable Immunity

    This week on Reprogrammed, Jack and Annie tackle a key limitation in CAR T cell therapy for solid tumors: poor trafficking to the tumor site. Centered on the 2010 study by Craddock et al., this episode explores how engineering T cells to express the chemokine receptor CCR2b—matching the tumor’s secretion of CCL2—can dramatically improve tumor infiltration without sacrificing cytotoxic function. Through in vitro migration assays and in vivo imaging in mouse models, the team unpacks how this strategy adds a modular “navigation” system to CAR T cells, allowing them to home in on their targets more effectively. With references to past episodes on co-stimulatory signaling, persistence, and dual-antigen targeting, this episode expands the design philosophy of CAR T therapy from “stronger” to “smarter.” Annie and Jack also look ahead to next week’s discussion of split-signal CARs that promise greater safety through precision control—bringing us closer to truly programmable immunity.

    15 min

  8. 17 de fev.

    Rational Design for persistence

    In this episode, we examine the work of Roselli et al.1, who explore a critical frontier in CAR T cell engineering: how to build T cells that don’t just kill tumors effectively, but also survive, persist, and adapt in the complex and hostile environments characteristic of solid tumors and relapsing hematologic malignancies. Building on themes from earlier episodes—such as the impact of co-stimulatory domains (CD28 vs. 4-1BB), strategies to reduce tonic signaling (Eyquem et al.), and optimizing cytokine support (IL-15)—this paper asks: Can we combine the best aspects of multiple co-stimulatory signals into a single CAR design? And, can dual-antigen targeting reduce the likelihood of tumor escape? Roselli et al. engineer several new CARs that incorporate both 4-1BB (for metabolic fitness and longevity) and a modified version of CD28 (mut06) designed to reduce exhaustion while retaining strong activation. They also explore tandem CARs targeting both CD19 and CD20, to limit the risk of antigen escape—a known challenge with CD19-directed therapies. Using the xCelligence platform, in vivo models, and transcriptional profiling, they show that these dual co-stimulatory CARs outperform their single-signal counterparts in terms of cytotoxicity, expansion, cytokine production, and resistance to exhaustion. The final experiments confirm that dual-antigen targeting not only delays relapse but also increases T cell persistence and flexibility, especially in tumors with heterogeneous antigen expression. In the broader arc of this podcast, this paper illustrates the field’s move toward rational CAR design and continuous improvement—combining lessons from receptor architecture, signaling dynamics, immune memory, and tumor evolution to create therapies that are both powerful and durable.

    25 min
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Sobre

Reprogrammed in a biotechnology podcast that explores a new topic every season through examining a series of seminal papers. This podcast supports a Selected Topics in Biotechnology course at the University of Kansas' Edwards Campus - but you don't need to be in that course to listen!

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