Dr. Daniel J. Siegwart is an Associate Professor in the Department of Biochemistry and the Simmons Comprehensive Cancer Center (SCCC) at UT Southwestern Medical Center (Dallas, Texas, U.S.A.). He is also the co-director for the Chemistry and Cancer Program within the National Cancer Institute-designated SCCC. He received a B.S. in Biochemistry from Lehigh University in 2003, and a Ph.D. in Chemistry from Carnegie Mellon University (CMU) in 2008 under the supervision of University Professor Krzysztof Matyjaszewski. During his graduate studies, he received the Joseph A. Solomon Memorial Fellowship in Chemistry at CMU and was a National Science Foundation East Asia and Pacific Summer Institutes Fellow at The University of Tokyo in 2006 with Prof. Kazunori Kataoka. He then completed a National Institutes of Health NRSA-sponsored Postdoctoral Fellowship at Massachusetts Institute of Technology with Institute Professor Robert Langer (2008-2012).
The central goal of the Siegwart Research Group is to use materials chemistry to solve challenges in disease therapy and diagnosis. In particular, they are focused on the development of new materials that can deliver genetic medicines to treat cancer and genetic diseases. An array of coding and non-coding nucleic acids can now be used as therapeutics (siRNA, miRNA, tRNA, mRNA, DNA, CRISPR RNAs, gene editors) because they are able to manipulate and edit expression of the essential genes that drive disease development and progression. However, the success of genetic therapies has been limited by the difficulty of delivering these highly anionic biomacromolecular drugs into cells.
The Siegwart Lab aims to discover and define the critical physical and chemical properties of synthetic carriers required for therapeutic delivery of small (e.g. ~22 base pair miRNA) to large (e.g. ~5,000 nucleotide mRNA) RNAs. They were the first to report in vivo CRISPR/Cas gene editing using non-viral carriers. They have designed synthetic carriers for various genome editors and applied these technologies for correction of genetic diseases. They have focused on hepatic and extrahepatic delivery for organ and cell specific protein delivery, gene delivery, and gene editing. They developed Selective Organ Targeting (SORT) lipid nanoparticles (LNPs), which was named in Nature's "Seven technologies to watch in 2022."
They aim to globally understand how the physical and chemical properties of materials affect interactions with biological systems in vitro and in vivo in the context of improving cancer and genetic disease therapies. Their research is grounded in chemical design and takes advantage of the unique opportunities for collaborative research at UTSW Medical Center. They ultimately aspire to utilize chemistry and engineering to make a beneficial impact on human health.
- Lehigh University (2003), Biochemistry
- Graduate School
- Carnegie Mellon University (2005), Chemistry
- Graduate School
- Carnegie Mellon University (2008), Chemistry
- On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles.
- Dilliard SA, Cheng Q, Siegwart DJ, Proc Natl Acad Sci U S A 2021 Dec 118 52
- Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR-Cas gene editing.
- Liu S, Cheng Q, Wei T, Yu X, Johnson LT, Farbiak L, Siegwart DJ, Nat Mater 2021 May 20 5 701-710
- Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing.
- Wei T, Cheng Q, Min YL, Olson EN, Siegwart DJ, Nat Commun 2020 06 11 1 3232
- Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing.
- Cheng Q, Wei T, Farbiak L, Johnson LT, Dilliard SA, Siegwart DJ, Nat Nanotechnol 2020 04 15 4 313-320
- Non-Viral CRISPR/Cas Gene Editing In Vitro and In Vivo Enabled by Synthetic Nanoparticle Co-Delivery of Cas9 mRNA and sgRNA.
- Miller JB, Zhang S, Kos P, Xiong H, Zhou K, Perelman SS, Zhu H, Siegwart DJ Angew. Chem. Int. Ed. Engl. 2016 Dec
- Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model.
- Zhou K, Nguyen LH, Miller JB, Yan Y, Kos P, Xiong H, Li L, Hao J, Minnig JT, Zhu H, Siegwart DJ Proc. Natl. Acad. Sci. U.S.A. 2016 Jan 113 3 520-5
- Rapid synthesis of a lipocationic polyester library via ring-opening polymerization of functional valerolactones for efficacious siRNA delivery
- Jing Hao, Petra Kos, Kejin Zhou, Jason B. Miller, Lian Xue, Yunfeng Yan, Hu Xiong, Sussana Elkassih, and Daniel J. Siegwart* Journal of the American Chemical Society 2015 137 9206-9209
- In vivo CRISPR screening identifies BAZ2 chromatin remodelers as druggable regulators of mammalian liver regeneration.
- Jia Y, Li L, Lin YH, Gopal P, Shen S, Zhou K, Yu X, Sharma T, Zhang Y, Siegwart DJ, Ready JM, Zhu H, Cell Stem Cell 2022 Jan
- Zwitterionic Phospholipidation of Cationic Polymers Facilitates Systemic mRNA Delivery to Spleen and Lymph Nodes.
- Liu S, Wang X, Yu X, Cheng Q, Johnson LT, Chatterjee S, Zhang D, Lee SM, Sun Y, Lin TC, Liu JL, Siegwart DJ, J Am Chem Soc 2021 Dec 143 50 21321-21330
- All-In-One Dendrimer-Based Lipid Nanoparticles Enable Precise HDR-Mediated Gene Editing In Vivo.
- Farbiak L, Cheng Q, Wei T, Álvarez-Benedicto E, Johnson LT, Lee S, Siegwart DJ, Adv Mater 2021 Jun e2006619
Honors & Awards
- American Institute for Medical and Biological Engineering College of Fellows
- W. Ray Wallace Distinguished Chair in Molecular Oncology Research
- Chinese Institute of Engineers Special Recognition Award
- Gilliam Fellow for Advanced Study (advisor-student pair)
- Biomaterials Science Emerging Investigator
- Young Innovator Award in Nanobiotechnology
- American Cancer Society Research Scholar
- Friends of the Comprehensive Cancer Center Award
- CPRIT Scholar Award
- Ruth L. Kirschstein National Research Service Award (NRSA) F32 Postdoctoral Fellowship
- East Asia and Pacific Summer Institutes (EAPSI) Fellowship
- The Joseph S. Solomon Memorial Fellowship in Chemistry
- Chemistry Department Research Honors
- Chair of Scientific Advisory Board at Recode Therapeutics (2022)
- Co-Founder Recode Therapeutics (2015-2015)
- Invivo Therapeutics Consultant (2010-2013)
- Member of Scientific Advisory Board at Tome Biosciences (2022)
- Mirna Therapeutics Consultant (2014-2016)
- NSF EAPSI Research Fellow Department of Materials Engineering (2006-2006)
- Recode Therapeutics Consultant (2017)
- Synthetic Chemistry Intern (2002-2002)