# Topics and Trends in Most Cited RNA Interference and Gene Delivery Papers, Class of 2026

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## What topics and trends defined most-cited RNA Interference and Gene Delivery research in the Class of 2026?

RNA interference and gene delivery research is anchored by lipid nanoparticles (50%) and ionizable lipids (22%). The Class of 2026 highlights a strong shift toward crossing the blood-brain barrier (16%), AI-assisted in silico screening (8%), and high-throughput vector discovery, while interest in general mRNA vaccines (6%) continues to decline.

## At a glance

| Fact | Value |
| --- | --- |
| Field | RNA Interference and Gene Delivery |
| Cohort label | Class of 2026 (2024 publications) |
| Papers analyzed | 9,649 |
| Papers ranked | 20 |
| Top topics in ranked papers | Lipid nanoparticles, Ionizable lipids, mRNA delivery, Blood-brain barrier, Extracellular vesicles (EVs) |
| Publication window | Jan 1, 2024 – Dec 31, 2024 |
| Eligibility | Research articles; reviews excluded |
| Citation window | 18 months post-publication |
| 18m citation range | 82–169 |
| Data source | OpenAlex · Retrieved Jul 2026 |
| License | CC BY 4.0 |

## Rankings

| Rank | Title | Authors | Corresponding authors | Affiliation | Journal | 18m citations | DOI |
| ---: | --- | --- | --- | --- | --- | ---: | --- |
| 1 | Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation | Kexin Su, Lu Shi, Tao Sheng, Xinxin Yan, Lixin Lin, Chaoyang Meng, Shiqi Wu, Yuxuan Chen, Yao Zhang, Chaorong Wang, Zichuan Wang, Junjie Qiu, Jiahui Zhao, Tengfei Xu, Yuan Ping, Zhen Gu, Shuai Liu | Ping Yuan, Zhen Gu, Shuai Liu | Zhejiang University, China | Nature Communications | 169 | 10.1038/s41467-024-50093-7 |
| 2 | Artificial intelligence-driven rational design of ionizable lipids for mRNA delivery | Wei Wang, Kepan Chen, Ting Jiang, Yiyang Wu, Zheng Wu, Hang Ying, Hang Yu, Jing Lu, Jinzhong Lin, Defang Ouyang | Jinzhong Lin, Defang Ouyang | University of Macau, China | Nature Communications | 156 | 10.1038/s41467-024-55072-6 |
| 3 | Direct cytosolic delivery of siRNA via cell membrane fusion using cholesterol-enriched exosomes | Yan Zhuo, Zhen Luo, Zhu Zhu, Jie Wang, Xiang Li, Zhuan Zhang, Cong Guo, Bingqi Wang, Di Nie, Yong Gan, Guoqing Hu, Miaorong Yu | Yong Gan, Guoqing Hu, Miaorong Yu | Chinese Academy of Sciences, China | Nature Nanotechnology | 126 | 10.1038/s41565-024-01785-0 |
| 4 | AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery | Yue Xu, Shihao Ma, Haotian Cui, Jingan Chen, Shufen Xu, Fanglin Gong, Alex Golubovic, Muye Zhou, Kevin Chang Wang, Andrew Varley, Rick Xing Ze Lu, Bo Wang, Bowen Li | Bo Wang, Bowen Li | University of Toronto, Canada | Nature Communications | 119 | 10.1038/s41467-024-50619-z |
| 5 | Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy | Jacob Witten, Idris Raji, Rajith S Manan, Emily Beyer, Sandra Bartlett, Yinghua Tang, Mehrnoosh Ebadi, Junying Lei, Dien Nguyen, Favour Oladimeji, Allen Yujie Jiang, Elise MacDonald, Yizong Hu, Haseeb Mughal, Ava Self, Evan Collins, Ziying Yan, John F Engelhardt, Robert Langer, Daniel G Anderson | Daniel G. Anderson | Massachusetts Institute of Technology, United States | Nature Biotechnology | 119 | 10.1038/s41587-024-02490-y |
| 6 | Accelerating ionizable lipid discovery for mRNA delivery using machine learning and combinatorial chemistry | Bowen Li, Idris O Raji, Akiva G R Gordon, Lizhuang Sun, Theresa M Raimondo, Favour A Oladimeji, Allen Y Jiang, Andrew Varley, Robert S Langer, Daniel G Anderson | Bowen Li, Daniel G. Anderson | Massachusetts Institute of Technology, United States | Nature Materials | 115 | 10.1038/s41563-024-01867-3 |
| 7 | In vivo editing of lung stem cells for durable gene correction in mice | Yehui Sun, Sumanta Chatterjee, Xizhen Lian, Zachary Traylor, Sandhya R Sattiraju, Yufen Xiao, Sean A Dilliard, Yun-Chieh Sung, Minjeong Kim, Sang M Lee, Stephen Moore, Xu Wang, Di Zhang, Shiying Wu, Pratima Basak, Jialu Wang, Jing Liu, Rachel J Mann, David F LePage, Weihong Jiang, Shadaan Abid, Mirko Hennig, Anna Martinez, Brandon A Wustman, David J Lockhart, Raksha Jain, Ronald A Conlon, Mitchell L Drumm, Craig A Hodges, Daniel J Siegwart | Yehui Sun, Sumanta Chatterjee, Daniel J. Siegwart | The University of Texas Southwestern Medical Center, United States | Science | 113 | 10.1126/science.adk9428 |
| 8 | Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain | Emily L Han, Sophia Tang, Dongyoon Kim, Amanda M Murray, Kelsey L Swingle, Alex G Hamilton, Kaitlin Mrksich, Marshall S Padilla, Rohan Palanki, Jacqueline J Li, Michael J Mitchell | Michael J. Mitchell | University of Pennsylvania, United States | Nano Letters | 113 | 10.1021/acs.nanolett.4c05186 |
| 9 | Charge-assisted stabilization of lipid nanoparticles enables inhaled mRNA delivery for mucosal vaccination | Shuai Liu, Yixing Wen, Xinzhu Shan, Xinghuan Ma, Chen Yang, Xingdi Cheng, Yuanyuan Zhao, Jingjiao Li, Shiwei Mi, Haonan Huo, Wei Li, Ziqiong Jiang, Yijia Li, Jiaqi Lin, Lei Miao, Xueguang Lu | Xueguang Lu | Chinese Academy of Sciences, China | Nature Communications | 108 | 10.1038/s41467-024-53914-x |
| 10 | Durable and efficient gene silencing in vivo by hit-and-run epigenome editing | Martino Alfredo Cappelluti, Valeria Mollica Poeta, Sara Valsoni, Piergiuseppe Quarato, Simone Merlin, Ivan Merelli, Angelo Lombardo | Angelo Lombardo | IRCCS San Raffaele Scientific Institute, Italy | Nature | 105 | 10.1038/s41586-024-07087-8 |
| 11 | Enhancing in situ cancer vaccines using delivery technologies | Ningqiang Gong, Mohamad-Gabriel Alameh, Rakan El-Mayta, Lulu Xue, Drew Weissman, Michael J Mitchell | Drew Weissman, Michael J. Mitchell | University of Pennsylvania, United States | Nature Reviews Drug Discovery | 101 | 10.1038/s41573-024-00974-9 |
| 12 | An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery | Qin Huang, Ken Y Chan, Jason Wu, Nuria R Botticello-Romero, Qingxia Zheng, Shan Lou, Casey Keyes, Alexander Svanbergsson, Jencilin Johnston, Allan Mills, Chin-Yen Lin, Pamela P Brauer, Gabrielle Clouse, Simon Pacouret, John W Harvey, Thomas Beddow, Jenna K Hurley, Isabelle G Tobey, Megan Powell, Albert T Chen, Andrew J Barry, Fatma-Elzahraa Eid, Yujia A Chan, Benjamin E Deverman | Qin Huang, Ken Y. Chan, Benjamin E. Deverman | Broad Institute of MIT and Harvard, United States | Science | 100 | 10.1126/science.adm8386 |
| 13 | Strategies to reduce the risks of mRNA drug and vaccine toxicity | Dimitrios Bitounis, Eric Jacquinet, Maximillian A Rogers, Mansoor M Amiji | Mansoor M. Amiji | Northeastern University, United States | Nature Reviews Drug Discovery | 98 | 10.1038/s41573-023-00859-3 |
| 14 | Targeting the transferrin receptor to transport antisense oligonucleotides across the mammalian blood-brain barrier | Scarlett J Barker, Mai B Thayer, Chaeyoung Kim, David Tatarakis, Matthew J Simon, Rebekah Dial, Lizanne Nilewski, Robert C Wells, Yinhan Zhou, Megan Afetian, Padma Akkapeddi, Alfred Chappell, Kylie S Chew, Johann Chow, Allisa Clemens, Claire B Discenza, Jason C Dugas, Chrissa Dwyer, Timothy Earr, Connie Ha, Yvonne S Ho, David Huynh, Edwin I Lozano, Srini Jayaraman, Wanda Kwan, Cathal Mahon, Michelle Pizzo, Yaneth Robles-Colmenares, Elysia Roche, Laura Sanders, Alexander Stergioulis, Raymond Tong, Hai Tran, Y Zuchero, Anthony A Estrada, Kapil Gadkar, Christopher M M Koth, Pascal E Sanchez, Robert G Thorne, Ryan J Watts, Thomas Sandmann, Lesley A Kane, Frank Rigo, Mark S Dennis, Joseph W Lewcock, Sarah L DeVos | Scarlett J. Barker, Mai B. Thayer, Chaeyoung Kim, David Tatarakis | Denali Therapeutics Inc., United States | Science Translational Medicine | 94 | 10.1126/scitranslmed.adi2245 |
| 15 | RNA aggregates harness the danger response for potent cancer immunotherapy | Hector R Mendez-Gomez, Anna DeVries, Paul Castillo, Christina von Roemeling, Sadeem Qdaisat, Brian D Stover, Chao Xie, Frances Weidert, Chong Zhao, Rachel Moor, Ruixuan Liu, Dhruvkumar Soni, Elizabeth Ogando-Rivas, Jonathan Chardon-Robles, James McGuiness, Dingpeng Zhang, Michael C Chung, Christiano Marconi, Stephen Michel, Arnav Barpujari, Gabriel W Jobin, Nagheme Thomas, Xiaojie Ma, Yodarlynis Campaneria, Adam Grippin, Aida Karachi, Derek Li, Bikash Sahay, Leighton Elliott, Timothy P Foster, Kirsten E Coleman, Rowan J Milner, W Gregory Sawyer, John A Ligon, Eugenio Simon, Brian Cleaver, Kristine Wynne, Marcia Hodik, Annette M Molinaro, Juan Guan, Patrick Kellish, Andria Doty, Ji-Hyun Lee, Tara Massini, Jesse L Kresak, Jianping Huang, Eugene I Hwang, Cassie Kline, Sheila Carrera-Justiz, Maryam Rahman, Sebastian Gatica, Sabine Mueller, Michael Prados, Ashley P Ghiaseddin, Natalie L Silver, Duane A Mitchell, Elias J Sayour | Hector R Mendez-Gomez | University of Florida, United States | Cell | 93 | 10.1016/j.cell.2024.04.003 |
| 16 | Peptide-functionalized, -assembled and -loaded nanoparticles in cancer therapy | Jingyuan Dai, Milad Ashrafizadeh, Amir Reza Aref, Gautam Sethi, Yavuz Nuri Ertas | Milad Ashrafizadeh, Gautam Sethi, Yavuz Nuri Ertaş | Northwest Missouri State University, United States | Drug Discovery Today | 92 | 10.1016/j.drudis.2024.103981 |
| 17 | Amine headgroups in ionizable lipids drive immune responses to lipid nanoparticles by binding to the receptors TLR4 and CD1d | Namit Chaudhary, Lisa N Kasiewicz, Alexandra N Newby, Mariah L Arral, Saigopalakrishna S Yerneni, Jilian R Melamed, Samuel T LoPresti, Katherine C Fein, Daria M Strelkova Petersen, Sushant Kumar, Rahul Purwar, Kathryn A Whitehead | Kathryn A. Whitehead | Carnegie Mellon University, United States | Nature Biomedical Engineering | 86 | 10.1038/s41551-024-01256-w |
| 18 | A bioswitchable delivery system for microRNA therapeutics based on a tetrahedral DNA nanostructure | Songhang Li, Taoran Tian, Tao Zhang, Yunfeng Lin, Xiaoxiao Cai | Xiaoxiao Cai | Sichuan University, China | Nature Protocols | 85 | 10.1038/s41596-024-01050-7 |
| 19 | Precision drug delivery to the central nervous system using engineered nanoparticles | Jingjing Gao, Ziting Xia, Swetharajan Gunasekar, Christopher Jiang, Jeffrey M. Karp, Nitin Joshi | Jingjing Gao, Jeffrey M. Karp, Nitin Joshi | University of Massachusetts, United States | Nature Reviews Materials | 82 | 10.1038/s41578-024-00695-w |
| 20 | Polymer-locking fusogenic liposomes for glioblastoma-targeted siRNA delivery and CRISPR–Cas gene editing | Yu Zhao, Jie Qin, Daohan Yu, Yuxiang Liu, Dan Song, Kaifu Tian, Hao Chen, Qile Ye, Xinyu Wang, Tianye Xu, Hanwen Xuan, Nan Sun, Wenbin Ma, Junzhe Zhong, Penggang Sun, Yu Song, Jingze Hu, Yunlei Zhao, Xintong Hou, Xiangqi Meng, Chuanlu Jiang, Jinquan Cai | Yu Zhao, Xintong Hou, Xiangqi Meng, Chuanlu Jiang, Jinquan Cai | The Second Affiliated Hospital of Harbin Medical University, China | Nature Nanotechnology | 82 | 10.1038/s41565-024-01769-0 |

## Topic trends

### What Topics Define the Class of 2026?

Lipid nanoparticle (LNP) formulation and optimization remain the absolute cornerstone of non-viral gene delivery research, present in 50% of the top-cited papers in the Class of 2026. Within this dominant paradigm, active investigation centres on custom lipid chemical engineering, with ionizable lipids (22%) and biodegradable lipids (8%) driving improved nucleic acid encapsulation, cellular internalization, and endosomal escape. Beyond standard systemic delivery, overcoming formidable physiological barriers has become a central focus; targeted transport across the blood-brain barrier (16%) and localized pulmonary delivery (8%) highlight the field's shift toward extrahepatic tissue targeting. In parallel, bio-inspired and biological nanocarriers, particularly extracellular vesicles (EVs, 14%), are gaining substantial traction as complementary platforms offering low immunogenicity and innate organ tropism. Finally, the methodological framework of gene delivery discovery is undergoing a modern transformation, as high-throughput screening platforms (10%) and in silico rational design (8%) replace traditional trial-and-error formulation methods to rapidly map structure-activity relationships.

*Leading research themes*

### How Did Topics Shift from the Class of 2025 to the Class of 2026?

Comparing the Class of 2025 to the Class of 2026 reveals a clear strategic pivot in gene delivery research: transitioning from post-pandemic systemic mRNA vaccines toward bio-targeted extrahepatic delivery, neurological therapeutics, and AI-accelerated formulation design. The most prominent thematic acceleration occurred in central nervous system (CNS) drug delivery, where interest in crossing the blood-brain barrier surged nearly three-fold from 6% in 2023 to 16% in 2024, accompanied by new applications targeting Parkinson's disease (6%). Simultaneously, delivery vector discovery has embraced advanced predictive methodologies: in silico screening expanded from 0% to 8%, AI-driven molecular design reached 4%, and high-throughput experimental screening increased five-fold from 2% to 10%. Conversely, general interest in broad mRNA vaccines contracted by half from 12% to 6%, while generic formulation studies gave way to targeted biophysical mechanisms such as membrane fusion (rising to 8%) and biodegradable lipid design (doubling to 8%). Together, these trends illustrate how the field is rapidly evolving beyond emergency vaccine technologies toward highly engineered, organ-specific genetic medicines.

*How topics shifted year over year*

## Cite this ranking

```
Pepkio Research Index (PRI). Topics and Trends in Most Cited RNA Interference and Gene Delivery Papers, Class of 2026. https://pri.pepkio.com/top-papers/rna-interference-and-gene-delivery/2026. Accessed 2026-07-21.

Zheng Su, Tinsley Li, Thematic Shifts in Early-High-Impact Cancer Genomics and Diagnostics Research: A Bibliometric and Semantic Analysis. bioRxiv 2026.07.04.736459; doi: https://doi.org/10.64898/2026.07.04.736459
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