The meeting presented Dr. Xiangxiang Shi's postdoctoral work at the intersection of biomaterials, drug delivery, and cancer immunotherapy, organized around three research stories: a pro-drug–tethered lipid nanoparticle (LNP) platform for co-delivering small-molecule inhibitors and mRNA, a lung-targeted intravenous mRNA vaccine strategy, and chemical barcoding for multiplexed nanoparticle screening. Dr. Shi... ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ ͏ ‌     ­ 👋 You've been invited to view this report because Robin D Terwilliger added Read to the meeting and wanted to share the recap with you. Qiangqiang Shi - Seminar Purdue AI‑Driven Biomolecular Design, Biotech & Computational Biology Position March 11, 2026 ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) map[action_items:[Crystal D O'Neal will analyze the collected serum and lung tissue samples for cytokine changes and T cell functional markers and report the results.] billing_plan:<nil> chapters:[map[chapter:Meeting opening and logistics topics:[Dr. Xiangxiang Shi presented research on precision nanomaterials for co-delivery of small-molecule drugs and mRNA for cancer immunotherapy.]] map[chapter:Speaker background and research overview topics:[]] map[chapter:Biological rationale and therapeutic strategy topics:[The team designed a pro-drug lipid that conjugates an IDO inhibitor to a lipid via a disulfide linkage for redox-triggered release. A 3-in-1 RNP approach co-delivering an IDO inhibitor and IL-12 mRNA aims to synergistically activate T cells while preventing exhaustion.]] map[chapter:Pro-drug lipid nanoparticle design, screening, and efficacy topics:[A lead pro-drug LNP from a 21-member library showed stability in physiologic conditions and triggered drug release under reducing conditions. Intratumoral delivery of the IL-12 pro-drug LNP induced high intratumoral T-cell infiltration, increased IFN-α/γ production, lowered exhaustion, and achieved complete tumor regression in a mouse colon cancer model.]] map[chapter:Lung-targeted LNP chemistry screening and candidates topics:[A separate chemistry screen produced lung-targeting LNP candidates; 1C18 showed strong lung transfection in mice.]] map[chapter:Lung organ and cell targeting, model setup topics:[The lung-targeting RNP transfects lung APCs, especially dendritic cells, enabling antigen presentation in the lung.]] map[chapter:RNP formulations and CD8 T-cell response comparison topics:[The 1C18 RNP produced the strongest CD8 T-cell response in lung tissue and outperformed the Moderna benchmark in this model. Multiple RNP formulations showed reduced T-cell exhaustion compared with the Moderna RNP in the reported assays. Co-loading IL-2 mRNA with antigen mRNA increased antigen-specific CD8 responses and tissue-resident memory T-cell responses in the lung.]] map[chapter:Adjuvant co-loading, memory, and tumor inhibition experiments topics:[Five-dose combination vaccination significantly reduced lung tumor burden in the aggressive lung cancer model used.]] map[chapter:Project summary and cancer immunity framing topics:[]] map[chapter:Barcode screening concept and chemical barcode design topics:[A chemical barcode system was developed that can be encoded into nanomaterials and read by mass spectrometry to quantify biodistribution of multiple nanoparticles in a single mouse.]] map[chapter:Barcode insertion, imaging, and compatibility with carriers topics:[Barcode chemistry can be incorporated into lipids, polymers, liposomes, and proteins without materially affecting delivery performance in preliminary tests.]] map[chapter:Library scale, machine learning optimization, and future applications topics:[The team proposes coupling barcode library synthesis with machine learning to optimize barcode-carrier structures for targeted RNA delivery and in vivo gene editing applications.]] map[chapter:Acknowledgements and Presentation Close topics:[]] map[chapter:Q&A — Lab Direction (Tool vs Application) topics:[The presenter will base her lab on a delivery platform with dual tracks: continued RMT-related optimization and higher-risk barcode-enabled innovations for gene delivery. The barcode delivery approach aims to enable predictable gene delivery with downstream applications in cancer immunotherapy, in situ vaccination, and in vivo gene editing.]] map[chapter:Q&A — Protein Barcoding Stability and Disease Modeling topics:[Chemical barcodes on proteins are unlikely to remain stable for a month in vivo; one to two weeks is more realistic based on the presenter’s assessment.]] map[chapter:Q&A — Combining Therapies and Tumor Model Dependence topics:[Therapeutic outcomes differed by tumor model; strong anti-tumor effect was observed in the colon cancer model but not in an autologous lung cancer model, so combination strategies will be model-dependent.]] map[chapter:Q&A — Automation, Assay Priorities, and In Vitro/In Vivo Metrics topics:[For automation and screening, the presenter prioritized mRNA transfection efficiency and nanoparticle room-temperature stability in vitro, and organ transduction efficiency and liver toxicity in vivo.]] map[chapter:Q&A — Dosing Strategy, Immune Feedback, and Functional T-cell Data topics:[The presenter is collecting serum and tissue samples to analyze cytokines and local immune environment and plans to test those data shortly.]]] content_tease_experiment_variant:<nil> distributor_names_string:Robin D Terwilliger email_access_invite_token:eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJraW5kIjoic2Vzc2lvbl9lbWFpbF9hY2Nlc3NfaW52aXRlIiwiZXhwaXJlc19hdCI6MTgwNDc5OTM5MjIxMywic2Vzc2lvbl9pZCI6IjAxS0tGNDA4SFBRS0VIQjNOSlBOSFQ3Q0hGIiwiZW1haWwiOiJibWVncmFkc3R1ZGVudHMtbGlzdEBlY24ucHVyZHVlLmVkdSJ9.FwdkHSmDDM0yNqVOtp3NAkcRiw75TgHlL1wSNcB6nF4 email_domain:<nil> email_verification_token:eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJraW5kIjoiZW1haWxfdmVyaWZpY2F0aW9uIiwiZXhwaXJlc19hdCI6MTgwNDc5OTM5MjIxMywiZW1haWwiOiJibWVncmFkc3R1ZGVudHMtbGlzdEBlY24ucHVyZHVlLmVkdSJ9.XgOe0pvg3Di68k785txemKf2TTlZ6k_2DXWqdpboTLY end_time_string:<nil> engagement_score:%!s(float64=68) has_thumbnail:%!s(bool=false) is_meeting_owner:%!s(bool=false) is_read_user:%!s(bool=false) is_subject_line_emoji_experiment:<nil> is_upsell_experiment:<nil> is_upsell_preview:<nil> is_zoom_upsell:<nil> key_questions:[How can the IDO–kynurenine–AHR pathway that drives T-cell exhaustion be prevented? If an IDO inhibitor and IL-12 mRNA are co-encapsulated in one RNP, will therapeutic effects be amplified? Are there carrier materials beyond standard RNP/lipid nanoparticles that can be used for gene delivery? Can multiple nanoparticles be screened in a single mouse using barcodes? How is the chemical barcode read once encoded into nanomaterials? Where will your future lab sit on the spectrum between tool development and applications? How stable are chemical barcodes on proteins in vivo — could they persist for a month? If you combine the two therapies that showed different survival outcomes, would you get intermediate or improved results? For automation and AI-guided screening, what minimal assays provide the most actionable information? Did you investigate dosing saturation or compensatory immune regulation with your aggressive vaccination strategy? What functional features and cytokine profiles do these T cells exhibit in the local environment?] late_by_string:0s live_notes_url:<nil> meeting_date_string:March 11, 2026 meeting_platform:teams meeting_title:Qiangqiang Shi - Seminar Purdue AI‑Driven Biomolecular Design, Biotech & Computational Biology Position metrics_level:full num_domain_users:<nil> num_recommendations:<nil> on_time:%!s(bool=true) overall_score:%!s(float64=75) raw_meeting_end_time:2026-03-11T20:04:22 raw_meeting_start_time:2026-03-11T19:00:00 raw_session_data_expiration_date:Apr 10 recipient_has_meeting_recap_enabled:%!s(bool=false) remaining_reports:<nil> report_quota:<nil> report_url:https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... rss_vanity_id:<nil> search_copilot_upsell_content:Crystal D O'Neal will analyze the collected serum and lung tissue samples for cytokine changes and T cell functional markers and report the results. search_copilot_upsell_link_placeholder:Crystal%20D%20O%27Neal%20will%20analyze%20the%20collected%20serum%20and%20lung%20tissue%20samples%20for%20cytokine%20changes%20and%20T%20cell%20functional%20markers%20and%20report%20the%20results. search_copilot_upsell_variant:sc_upsell_3 send_recap_to_participants:<nil> sentiment_score:%!s(float64=81) session_id:01KKF408HPQKEHB3NJPNHT7CHF sgParameters:map[replyTo:rterwill@purdue.edu templateID:d-27268193e8204d13bd4207d81aabe6c2 templateName:Participant Meeting Recap 3/6/2026 - Revert Action Items Section versionID:066ab4f9-a894-4a56-b6e5-44efc96f9e75] start_time_string:<nil> subject:<nil> summary:The meeting presented Dr. Xiangxiang Shi's postdoctoral work at the intersection of biomaterials, drug delivery, and cancer immunotherapy, organized around three research stories: a pro-drug–tethered lipid nanoparticle (LNP) platform for co-delivering small-molecule inhibitors and mRNA, a lung-targeted intravenous mRNA vaccine strategy, and chemical barcoding for multiplexed nanoparticle screening. Dr. Shi... summary_paragraphs:[The meeting presented Dr. Xiangxiang Shi's postdoctoral work at the intersection of biomaterials, drug delivery, and cancer immunotherapy, organized around three research stories: a pro-drug–tethered lipid nanoparticle (LNP) platform for co-delivering small-molecule inhibitors and mRNA, a lung-targeted intravenous mRNA vaccine strategy, and chemical barcoding for multiplexed nanoparticle screening. Dr. Shi...] talk_time:<nil> talking_pace:<nil> top_talkers:[map[name:Crystal D O'Neal rank:%!s(float64=1) talk_time_percentage:%!s(float64=100) talk_time_string:1h 5m 43s] map[name:Pengfei Wu rank:%!s(float64=2) talk_time_percentage:%!s(float64=0) talk_time_string:4s]] topics:[Dr. Xiangxiang Shi presented research on precision nanomaterials for co-delivery of small-molecule drugs and mRNA for cancer immunotherapy. A 3-in-1 RNP approach co-delivering an IDO inhibitor and IL-12 mRNA aims to synergistically activate T cells while preventing exhaustion. The team designed a pro-drug lipid that conjugates an IDO inhibitor to a lipid via a disulfide linkage for redox-triggered release. A lead pro-drug LNP from a 21-member library showed stability in physiologic conditions and triggered drug release under reducing conditions. Intratumoral delivery of the IL-12 pro-drug LNP induced high intratumoral T-cell infiltration, increased IFN-α/γ production, lowered exhaustion, and achieved complete tumor regression in a mouse colon cancer model. A separate chemistry screen produced lung-targeting LNP candidates; 1C18 showed strong lung transfection in mice. The lung-targeting RNP transfects lung APCs, especially dendritic cells, enabling antigen presentation in the lung. The 1C18 RNP produced the strongest CD8 T-cell response in lung tissue and outperformed the Moderna benchmark in this model. Multiple RNP formulations showed reduced T-cell exhaustion compared with the Moderna RNP in the reported assays. Co-loading IL-2 mRNA with antigen mRNA increased antigen-specific CD8 responses and tissue-resident memory T-cell responses in the lung. Five-dose combination vaccination significantly reduced lung tumor burden in the aggressive lung cancer model used. A chemical barcode system was developed that can be encoded into nanomaterials and read by mass spectrometry to quantify biodistribution of multiple nanoparticles in a single mouse. Barcode chemistry can be incorporated into lipids, polymers, liposomes, and proteins without materially affecting delivery performance in preliminary tests. The team proposes coupling barcode library synthesis with machine learning to optimize barcode-carrier structures for targeted RNA delivery and in vivo gene editing applications. The presenter will base her lab on a delivery platform with dual tracks: continued RMT-related optimization and higher-risk barcode-enabled innovations for gene delivery. The barcode delivery approach aims to enable predictable gene delivery with downstream applications in cancer immunotherapy, in situ vaccination, and in vivo gene editing. Chemical barcodes on proteins are unlikely to remain stable for a month in vivo; one to two weeks is more realistic based on the presenter’s assessment. Therapeutic outcomes differed by tumor model; strong anti-tumor effect was observed in the colon cancer model but not in an autologous lung cancer model, so combination strategies will be model-dependent. For automation and screening, the presenter prioritized mRNA transfection efficiency and nanoparticle room-temperature stability in vitro, and organ transduction efficiency and liver toxicity in vivo. The presenter is collecting serum and tissue samples to analyze cytokines and local immune environment and plans to test those data shortly.] used_reports:<nil> zoom_reauthentication_required:<nil>] Access this meeting report ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) Account creation required. This is your personal link, please do not forward this email to others. View Report ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) Recap Chapters & Topics 🔒 Upgrade to view chapters & topics ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) Chapters & Topics 🔒 Upgrade to view chapters & topics ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) Chapters & Topics • Meeting opening and logistics • map[action_items:[Crystal D O'Neal will analyze the collected serum and lung tissue samples for cytokine changes and T cell functional markers and report the results.] billing_plan:<nil> chapters:[map[chapter:Meeting opening and logistics topics:[Dr. Xiangxiang Shi presented research on precision nanomaterials for co-delivery of small-molecule drugs and mRNA for cancer immunotherapy.]] map[chapter:Speaker background and research overview topics:[]] map[chapter:Biological rationale and therapeutic strategy topics:[The team designed a pro-drug lipid that conjugates an IDO inhibitor to a lipid via a disulfide linkage for redox-triggered release. A 3-in-1 RNP approach co-delivering an IDO inhibitor and IL-12 mRNA aims to synergistically activate T cells while preventing exhaustion.]] map[chapter:Pro-drug lipid nanoparticle design, screening, and efficacy topics:[A lead pro-drug LNP from a 21-member library showed stability in physiologic conditions and triggered drug release under reducing conditions. Intratumoral delivery of the IL-12 pro-drug LNP induced high intratumoral T-cell infiltration, increased IFN-α/γ production, lowered exhaustion, and achieved complete tumor regression in a mouse colon cancer model.]] map[chapter:Lung-targeted LNP chemistry screening and candidates topics:[A separate chemistry screen produced lung-targeting LNP candidates; 1C18 showed strong lung transfection in mice.]] map[chapter:Lung organ and cell targeting, model setup topics:[The lung-targeting RNP transfects lung APCs, especially dendritic cells, enabling antigen presentation in the lung.]] map[chapter:RNP formulations and CD8 T-cell response comparison topics:[The 1C18 RNP produced the strongest CD8 T-cell response in lung tissue and outperformed the Moderna benchmark in this model. Multiple RNP formulations showed reduced T-cell exhaustion compared with the Moderna RNP in the reported assays. Co-loading IL-2 mRNA with antigen mRNA increased antigen-specific CD8 responses and tissue-resident memory T-cell responses in the lung.]] map[chapter:Adjuvant co-loading, memory, and tumor inhibition experiments topics:[Five-dose combination vaccination significantly reduced lung tumor burden in the aggressive lung cancer model used.]] map[chapter:Project summary and cancer immunity framing topics:[]] map[chapter:Barcode screening concept and chemical barcode design topics:[A chemical barcode system was developed that can be encoded into nanomaterials and read by mass spectrometry to quantify biodistribution of multiple nanoparticles in a single mouse.]] map[chapter:Barcode insertion, imaging, and compatibility with carriers topics:[Barcode chemistry can be incorporated into lipids, polymers, liposomes, and proteins without materially affecting delivery performance in preliminary tests.]] map[chapter:Library scale, machine learning optimization, and future applications topics:[The team proposes coupling barcode library synthesis with machine learning to optimize barcode-carrier structures for targeted RNA delivery and in vivo gene editing applications.]] map[chapter:Acknowledgements and Presentation Close topics:[]] map[chapter:Q&A — Lab Direction (Tool vs Application) topics:[The presenter will base her lab on a delivery platform with dual tracks: continued RMT-related optimization and higher-risk barcode-enabled innovations for gene delivery. The barcode delivery approach aims to enable predictable gene delivery with downstream applications in cancer immunotherapy, in situ vaccination, and in vivo gene editing.]] map[chapter:Q&A — Protein Barcoding Stability and Disease Modeling topics:[Chemical barcodes on proteins are unlikely to remain stable for a month in vivo; one to two weeks is more realistic based on the presenter’s assessment.]] map[chapter:Q&A — Combining Therapies and Tumor Model Dependence topics:[Therapeutic outcomes differed by tumor model; strong anti-tumor effect was observed in the colon cancer model but not in an autologous lung cancer model, so combination strategies will be model-dependent.]] map[chapter:Q&A — Automation, Assay Priorities, and In Vitro/In Vivo Metrics topics:[For automation and screening, the presenter prioritized mRNA transfection efficiency and nanoparticle room-temperature stability in vitro, and organ transduction efficiency and liver toxicity in vivo.]] map[chapter:Q&A — Dosing Strategy, Immune Feedback, and Functional T-cell Data topics:[The presenter is collecting serum and tissue samples to analyze cytokines and local immune environment and plans to test those data shortly.]]] content_tease_experiment_variant:<nil> distributor_names_string:Robin D Terwilliger email_access_invite_token:eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJraW5kIjoic2Vzc2lvbl9lbWFpbF9hY2Nlc3NfaW52aXRlIiwiZXhwaXJlc19hdCI6MTgwNDc5OTM5MjIxMywic2Vzc2lvbl9pZCI6IjAxS0tGNDA4SFBRS0VIQjNOSlBOSFQ3Q0hGIiwiZW1haWwiOiJibWVncmFkc3R1ZGVudHMtbGlzdEBlY24ucHVyZHVlLmVkdSJ9.FwdkHSmDDM0yNqVOtp3NAkcRiw75TgHlL1wSNcB6nF4 email_domain:<nil> email_verification_token:eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJraW5kIjoiZW1haWxfdmVyaWZpY2F0aW9uIiwiZXhwaXJlc19hdCI6MTgwNDc5OTM5MjIxMywiZW1haWwiOiJibWVncmFkc3R1ZGVudHMtbGlzdEBlY24ucHVyZHVlLmVkdSJ9.XgOe0pvg3Di68k785txemKf2TTlZ6k_2DXWqdpboTLY end_time_string:<nil> engagement_score:%!s(float64=68) has_thumbnail:%!s(bool=false) is_meeting_owner:%!s(bool=false) is_read_user:%!s(bool=false) is_subject_line_emoji_experiment:<nil> is_upsell_experiment:<nil> is_upsell_preview:<nil> is_zoom_upsell:<nil> key_questions:[How can the IDO–kynurenine–AHR pathway that drives T-cell exhaustion be prevented? If an IDO inhibitor and IL-12 mRNA are co-encapsulated in one RNP, will therapeutic effects be amplified? Are there carrier materials beyond standard RNP/lipid nanoparticles that can be used for gene delivery? Can multiple nanoparticles be screened in a single mouse using barcodes? How is the chemical barcode read once encoded into nanomaterials? Where will your future lab sit on the spectrum between tool development and applications? How stable are chemical barcodes on proteins in vivo — could they persist for a month? If you combine the two therapies that showed different survival outcomes, would you get intermediate or improved results? For automation and AI-guided screening, what minimal assays provide the most actionable information? Did you investigate dosing saturation or compensatory immune regulation with your aggressive vaccination strategy? What functional features and cytokine profiles do these T cells exhibit in the local environment?] late_by_string:0s live_notes_url:<nil> meeting_date_string:March 11, 2026 meeting_platform:teams meeting_title:Qiangqiang Shi - Seminar Purdue AI‑Driven Biomolecular Design, Biotech & Computational Biology Position metrics_level:full num_domain_users:<nil> num_recommendations:<nil> on_time:%!s(bool=true) overall_score:%!s(float64=75) raw_meeting_end_time:2026-03-11T20:04:22 raw_meeting_start_time:2026-03-11T19:00:00 raw_session_data_expiration_date:Apr 10 recipient_has_meeting_recap_enabled:%!s(bool=false) remaining_reports:<nil> report_quota:<nil> report_url:https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... rss_vanity_id:<nil> search_copilot_upsell_content:Crystal D O'Neal will analyze the collected serum and lung tissue samples for cytokine changes and T cell functional markers and report the results. search_copilot_upsell_link_placeholder:Crystal%20D%20O%27Neal%20will%20analyze%20the%20collected%20serum%20and%20lung%20tissue%20samples%20for%20cytokine%20changes%20and%20T%20cell%20functional%20markers%20and%20report%20the%20results. search_copilot_upsell_variant:sc_upsell_3 send_recap_to_participants:<nil> sentiment_score:%!s(float64=81) session_id:01KKF408HPQKEHB3NJPNHT7CHF sgParameters:map[replyTo:rterwill@purdue.edu templateID:d-27268193e8204d13bd4207d81aabe6c2 templateName:Participant Meeting Recap 3/6/2026 - Revert Action Items Section versionID:066ab4f9-a894-4a56-b6e5-44efc96f9e75] start_time_string:<nil> subject:<nil> summary:The meeting presented Dr. Xiangxiang Shi's postdoctoral work at the intersection of biomaterials, drug delivery, and cancer immunotherapy, organized around three research stories: a pro-drug–tethered lipid nanoparticle (LNP) platform for co-delivering small-molecule inhibitors and mRNA, a lung-targeted intravenous mRNA vaccine strategy, and chemical barcoding for multiplexed nanoparticle screening. Dr. Shi... summary_paragraphs:[The meeting presented Dr. Xiangxiang Shi's postdoctoral work at the intersection of biomaterials, drug delivery, and cancer immunotherapy, organized around three research stories: a pro-drug–tethered lipid nanoparticle (LNP) platform for co-delivering small-molecule inhibitors and mRNA, a lung-targeted intravenous mRNA vaccine strategy, and chemical barcoding for multiplexed nanoparticle screening. Dr. Shi...] talk_time:<nil> talking_pace:<nil> top_talkers:[map[name:Crystal D O'Neal rank:%!s(float64=1) talk_time_percentage:%!s(float64=100) talk_time_string:1h 5m 43s] map[name:Pengfei Wu rank:%!s(float64=2) talk_time_percentage:%!s(float64=0) talk_time_string:4s]] topics:[Dr. Xiangxiang Shi presented research on precision nanomaterials for co-delivery of small-molecule drugs and mRNA for cancer immunotherapy. A 3-in-1 RNP approach co-delivering an IDO inhibitor and IL-12 mRNA aims to synergistically activate T cells while preventing exhaustion. The team designed a pro-drug lipid that conjugates an IDO inhibitor to a lipid via a disulfide linkage for redox-triggered release. A lead pro-drug LNP from a 21-member library showed stability in physiologic conditions and triggered drug release under reducing conditions. Intratumoral delivery of the IL-12 pro-drug LNP induced high intratumoral T-cell infiltration, increased IFN-α/γ production, lowered exhaustion, and achieved complete tumor regression in a mouse colon cancer model. A separate chemistry screen produced lung-targeting LNP candidates; 1C18 showed strong lung transfection in mice. The lung-targeting RNP transfects lung APCs, especially dendritic cells, enabling antigen presentation in the lung. The 1C18 RNP produced the strongest CD8 T-cell response in lung tissue and outperformed the Moderna benchmark in this model. Multiple RNP formulations showed reduced T-cell exhaustion compared with the Moderna RNP in the reported assays. Co-loading IL-2 mRNA with antigen mRNA increased antigen-specific CD8 responses and tissue-resident memory T-cell responses in the lung. Five-dose combination vaccination significantly reduced lung tumor burden in the aggressive lung cancer model used. A chemical barcode system was developed that can be encoded into nanomaterials and read by mass spectrometry to quantify biodistribution of multiple nanoparticles in a single mouse. Barcode chemistry can be incorporated into lipids, polymers, liposomes, and proteins without materially affecting delivery performance in preliminary tests. The team proposes coupling barcode library synthesis with machine learning to optimize barcode-carrier structures for targeted RNA delivery and in vivo gene editing applications. The presenter will base her lab on a delivery platform with dual tracks: continued RMT-related optimization and higher-risk barcode-enabled innovations for gene delivery. The barcode delivery approach aims to enable predictable gene delivery with downstream applications in cancer immunotherapy, in situ vaccination, and in vivo gene editing. Chemical barcodes on proteins are unlikely to remain stable for a month in vivo; one to two weeks is more realistic based on the presenter’s assessment. Therapeutic outcomes differed by tumor model; strong anti-tumor effect was observed in the colon cancer model but not in an autologous lung cancer model, so combination strategies will be model-dependent. For automation and screening, the presenter prioritized mRNA transfection efficiency and nanoparticle room-temperature stability in vitro, and organ transduction efficiency and liver toxicity in vivo. The presenter is collecting serum and tissue samples to analyze cytokines and local immune environment and plans to test those data shortly.] used_reports:<nil> zoom_reauthentication_required:<nil>] See all 18 chapters → ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) Action Items • Crystal D O'Neal will analyze the collected serum and lung tissue samples for cytokine changes and T cell functional markers and report the results. • See all 1 action items → ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) Key Questions • How can the IDO–kynurenine–AHR pathway that drives T-cell exhaustion be prevented? • If an IDO inhibitor and IL-12 mRNA are co-encapsulated in one RNP, will therapeutic effects be amplified? See all 11 key questions → ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) Review notes ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) Work smarter, not harder Read makes meetings more effective and efficient with meeting recaps, transcripts, playback, personalized coaching, meeting recommendations, and more. Get started for free → ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) Need help? Visit the Support Center ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5Llcqxn... ) or contact us ( support@read.ai ). Unsubscribe ( https://u25608997.ct.sendgrid.net/asm/unsubscribe/?user_id=25608997&data=FSk... ) • Email Preferences ( https://u25608997.ct.sendgrid.net/ls/click?upn=u001.CrUrehIev9dAOd9CS5LlcqT6... ) Team at Read AI • 999 3rd Ave, Suite 3300, Seattle, WA 98104