Plug-and-play assembly of biodegradable ionizable lipids for potent mRNA delivery and gene editing in vivo Xuexiang Han, Ying Xu, Adele S. Ricciardi, Junchao Xu, Yan Xiang, et al. Proceedings of the National Academy of Sciences of the United States of America, 2026 mRNA-based gene editing therapeutics offer the potential to permanently cure diseases but are hindered by suboptimal delivery platforms. Here, we devise a robust combinatorial chemistry for the plug-and-play assembly of structurally diverse biodegradable ionizable lipids from amines/thiols and dialkyl maleates. After screening 500 ionizable lipids, we obtained structure−activity relationships essential for effective in vitro mRNA delivery with the help of machine learning. Furthermore, we identified a lead ionizable lipid candidate that produced potent lipid nanoparticles for the delivery of various gene editing tools in wild-type and genetically modified mice compared to literature and industry benchmark lipid nanoparticles. Mechanistically, our lipid nanoparticles show favorable physicochemical properties, which could synergistically contribute to the superior delivery performance. This study highlights the utility of this synthetic method as well as the generality of this platform for potent in vivo gene editing.
The Responsible Development of Adeno-Associated Virus Gene Therapies James M Wilson, Arthur L. Caplan Human Gene Therapy, 2025 Several unexpected fatalities in patients who received adeno-associated virus (AAV)-based gene therapies have recently occurred. These tragic events have cast a pall over the entire sector with some stakeholders suggesting that AAV is patently unsafe as a gene delivery platform and ought not to be pursued. This conclusion is not warranted.
In situ combinatorial synthesis of degradable branched lipidoids for systemic delivery of mRNA therapeutics and gene editors Xuexiang Han, Junchao Xu, Ying Xu, Mohamad-Gabriel Alameh, Lulu Xue, et al. Nature Communications, 2024 The ionizable lipidoid is a key component of lipid nanoparticles (LNPs). Degradable lipidoids containing extended alkyl branches have received tremendous attention, yet their optimization and investigation are underappreciated. Here, we devise an in situ construction method for the combinatorial synthesis of degradable branched (DB) lipidoids. We find that appending branch tails to inefficacious lipidoids via degradable linkers boosts mRNA delivery efficiency up to three orders of magnitude. Combinatorial screening and systematic investigation of two libraries of DB-lipidoids reveal important structural criteria that govern their in vivo potency. The lead DB-LNP demonstrates robust delivery of mRNA therapeutics and gene editors into the liver. In a diet-induced obese mouse model, we show that repeated administration of DB-LNP encapsulating mRNA encoding human fibroblast growth factor 21 alleviates obesity and fatty liver. Together, we offer a construction strategy for high-throughput and cost-efficient synthesis of DB-lipidoids. This study provides insights into branched lipidoids for efficient mRNA delivery.
AB0238 Patient-centred approach to management of inflammatory arthritis was associated with improved satisfaction of care and perceived treatment benefit L Attipoe, S Virdee, J Greenan-Barrett, D Shah, A Cotton, J Guinto, ... Annals of the Rheumatic Diseases 77, 1301 , 2018 2018 Citations: 2
An AC coupled 10 Gb/s LVDS-compatible receiver with latched data biasing in 130 nm SiGe BiCMOS B Mathieu, JJ McCue, B Dupaix, VJ Patel, S Dooley, J Wilson, ... 2017 IEEE Compound Semiconductor Integrated Circuit Symposium (CSICS), 1-4 , 2017 2017 Citations: 2
Low voltage differential signal receiver with fully integrated AC coupling and bias latching J McCue, VJ Patel, W Khalil, B Dupaix, J Wilson, SR Dooley US Patent 9,698,735 , 2017 2017 Citations: 9
Transformer winding resistance tester test probe and method JC Wilson, R Ross US Patent 9,151,788 , 2015 2015 Citations: 1
Rolling Stock Specification for an Auto-Transformer Electrification System J Wilson Railway Electrification, 9 , 2014 2014
Toward millimeter-wave DACs: Challenges and opportunities W Khalil, J Wilson, B Dupaix, S Balasubramanian, GL Creech 2012 IEEE Compound Semiconductor Integrated Circuit Symposium (CSICS), 1-4 , 2012 2012 Citations: 19
Ultimate transmission S Balasubramanian, S Boumaiza, H Sarbishaei, T Quach, P Orlando, ... IEEE Microwave Magazine 13 (1), 64-82 , 2012 2012 Citations: 71
终极传输 S Balasubramanian, S Boumaiza, H Sarbishaei, T Quach, P Orlando, ... IEEE microwave magazine, 64 , 2012 2012
Systematic analysis of interleaved digital-to-analog converters S Balasubramanian, G Creech, J Wilson, SM Yoder, JJ McCue, ... IEEE Transactions on Circuits and Systems II: Express Briefs 58 (12), 882-886 , 2011 2011 Citations: 78
Sensing and latching circuit for memory arrays J Wilson, G Hoyer US Patent 7,995,411 , 2011 2011 Citations: 4
40 GSps, 6-bit RF DAC Design Report JE Wilson 2011
Memory sensing and latching circuit J Wilson, G Hoyer US Patent 7,760,568 , 2010 2010 Citations: 2
Method for authenticating radio frequency identification JC Wilson, G Andrechak US Patent App. 12/216,456 , 2010 2010 Citations: 18
Key identification system and form fitting label and method of manufacture JC Wilson US Patent 7,587,848 , 2009 2009 Citations: 10
Input match and load tank digital calibration of an inductively degenerated CMOS LNA J Wilson, M Ismail Integration 42 (1), 3-9 , 2009 2009 Citations: 36
Aerospace composite-rotor induction motors JC Wilson, EA Erdelyi, RE Hopkins IEEE Transactions on Aerospace, 18-23 , 2007 2007 Citations: 25
Method and apparatus for performing benefit transactions using a portable intergrated circuit device B Lee, J Wilson US Patent App. 11/767,919 , 2007 2007 Citations: 6
Method and apparatus for performing benefit transactions using a portable integrated circuit device B Lee, JC Wilson US Patent 7,234,638 , 2007 2007 Citations: 43
Application of motor control centers with molded-case circuit breakers in systems with high fault capability JC Wilson, HS Robinson IEEE Transactions on Industry Applications, 66-80 , 2007 2007 Citations: 2
The chip-peak detectors for multistandard wireless receivers SB Park, JE Wilson, M Ismail IEEE Circuits and Devices Magazine 22 (6), 6-9 , 2007 2007 Citations: 75
MOST CITED SCHOLAR PUBLICATIONS
Portable electronic data storage and retreival system for group data J Wilson, B Lee US Patent App. 10/760,172 , 2005 2005 Citations: 340
A single-chip CMOS transceiver for 802.11 a/b/g wireless LANs R Ahola, A Aktas, J Wilson, KR Rao, F Jonsson, I Hyyrylainen, A Brolin, ... IEEE Journal of Solid-State Circuits 39 (12), 2250-2258 , 2004 2004 Citations: 123
Internal protection circuit for electrically driven device JR D'Entremont, HH Fraser Jr, JC Wilson US Patent 5,200,872 , 1993 1993 Citations: 90
Systematic analysis of interleaved digital-to-analog converters S Balasubramanian, G Creech, J Wilson, SM Yoder, JJ McCue, ... IEEE Transactions on Circuits and Systems II: Express Briefs 58 (12), 882-886 , 2011 2011 Citations: 78
The chip-peak detectors for multistandard wireless receivers SB Park, JE Wilson, M Ismail IEEE Circuits and Devices Magazine 22 (6), 6-9 , 2007 2007 Citations: 75
Ultimate transmission S Balasubramanian, S Boumaiza, H Sarbishaei, T Quach, P Orlando, ... IEEE Microwave Magazine 13 (1), 64-82 , 2012 2012 Citations: 71
A CMOS RF front-end for a multistandard WLAN receiver KR Rao, J Wilson, M Ismail IEEE Microwave and Wireless Components Letters 15 (5), 321-323 , 2005 2005 Citations: 56
Ground fault protector with arcing fault indicator JT Wilson, JC Wilson US Patent 3,911,323 , 1975 1975 Citations: 54
Methods and systems for improved integrated circuit functional simulation J Wilson, K Imboden, D Gold US Patent App. 10/927,810 , 2005 2005 Citations: 51
A single chip CMOS transceiver for 802.11 a/b/g WLANs R Ahola, A Aktas, J Wilson, KR Rao, F Jonsson, I Hyyrylainen, A Brolin, ... 2004 IEEE International Solid-State Circuits Conference (IEEE Cat. No … , 2004 2004 Citations: 45
Radio design in nanometer technologies M Ismail, DR de Llera González Springer , 2006 2006 Citations: 44
Method and apparatus for performing benefit transactions using a portable integrated circuit device B Lee, JC Wilson US Patent 7,234,638 , 2007 2007 Citations: 43
Input match and load tank digital calibration of an inductively degenerated CMOS LNA J Wilson, M Ismail Integration 42 (1), 3-9 , 2009 2009 Citations: 36
Method, software and device for managing patient medical records in a universal format using USB flash drive and radio telephone auto dialer and siren J Wilson US Patent App. 11/450,151 , 2007 2007 Citations: 31
Multi standard transceiver architecture for wlan A Aktas, K Rama, J Wilson US Patent App. 10/478,467 , 2004 2004 Citations: 30
Containment device for retaining semiconductor wafers L Lewis, KT Hirose, J Wilson, J Dove, M Hayden US Patent 6,193,068 , 2001 2001 Citations: 26
Aerospace composite-rotor induction motors JC Wilson, EA Erdelyi, RE Hopkins IEEE Transactions on Aerospace, 18-23 , 2007 2007 Citations: 25
End-winding leakage of high-speed alternators by three-dimensional field determination MS Sarma, JC Wilson, PJ Lawrenson, AL Jokl IEEE Transactions on Power Apparatus and Systems, 465-477 , 2007 2007 Citations: 25
Toward millimeter-wave DACs: Challenges and opportunities W Khalil, J Wilson, B Dupaix, S Balasubramanian, GL Creech 2012 IEEE Compound Semiconductor Integrated Circuit Symposium (CSICS), 1-4 , 2012 2012 Citations: 19
Method for authenticating radio frequency identification JC Wilson, G Andrechak US Patent App. 12/216,456 , 2010 2010 Citations: 18
RESEARCH OUTPUTS (PATENTS, SOFTWARE, PUBLICATIONS, PRODUCTS)
A single-chip CMOS transceiver for 802.11 a/b/g wireless LANs
Portable electronic data storage and retreival system for group data