Dominik Witzigmann
University of British Columbia
Genetic enhancementBiophysicsTargeted drug deliveryGene deliveryNanomedicineNanoparticleNanocarriersLiposomeChemistryMaterials scienceIn vitroIn vivoZebrafishDrug deliveryDrugCancer researchBiochemistryComputational biologyMedicineCell biologyPharmacology
49Publications
16H-index
1,918Citations
Publications 48
Newest
#1Jayesh A. Kulkarni (UBC: University of British Columbia)H-Index: 14
#2Dominik Witzigmann (UBC: University of British Columbia)H-Index: 16
Last. Roy van der Meel (TU/e: Eindhoven University of Technology)H-Index: 21
view all 0 authors...
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#1Dominik Witzigmann (University of Basel)H-Index: 16
#2Philip Grossen (University of Basel)H-Index: 8
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 18 authors...
Abstract Hepatocellular carcinoma (HCC) is related to increasing incidence rates and poor clinical outcomes due to lack of efficient treatment options and emerging resistance mechanisms. The aim of the present study is to exploit a non-viral gene therapy enabling the expression of the parvovirus-derived oncotoxic protein NS1 in HCC. This anticancer protein interacts with different cellular kinases mediating a multimodal host-cell death. Lipoplexes (LPX) designed to deliver a DNA expression plasm...
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#1Anthony Tam (UBC: University of British Columbia)H-Index: 11
#2Pascal Leclair (UBC: University of British Columbia)H-Index: 6
Last. Gurpreet K. Singhera (UBC: University of British Columbia)H-Index: 16
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Genome-wide association studies have shown that a gene variant in the Family with Sequence Similarity 13, Member A (FAM13A) is strongly associated with reduced lung function and the appearance of respiratory symptoms in patients with Chronic Obstructive Pulmonary Disease (COPD). A key player in smoking-induced tissue injury and airway remodeling is the transforming growth factor β1 (TGFβ1). To determine the role of FAM13A in TGFβ1 signaling, FAM13A-/- airway epithelial cells were generated using...
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#1Jayesh A. Kulkarni (UBC: University of British Columbia)H-Index: 14
#2Dominik WitzigmannH-Index: 16
Last. Roy van der Meel (TU/e: Eindhoven University of Technology)H-Index: 21
view all 7 authors...
The increasing number of approved nucleic acid therapeutics demonstrates the potential to treat diseases by targeting their genetic blueprints in vivo. Conventional treatments generally induce therapeutic effects that are transient because they target proteins rather than underlying causes. In contrast, nucleic acid therapeutics can achieve long-lasting or even curative effects via gene inhibition, addition, replacement or editing. Their clinical translation, however, depends on delivery technol...
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#1Tanja Rothgangl (UZH: University of Zurich)H-Index: 1
#2Melissa K. DennisH-Index: 1
Last. Gerald Schwank (UZH: University of Zurich)H-Index: 18
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Most known pathogenic point mutations in humans are C•G to T•A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs in the livers of mice and cynomolgus macaques for the reduction of blood low-density lipoprotein (LDL) levels. Lipid nanoparticle-based delivery of mRNA encoding an ABE and a single-guide RNA targeting PCSK9, a negative regulator of LDL, induced up to 67% editing (on average, 61%) in mice and up...
6 CitationsSource
#1Linde Schoenmaker (LEI: Leiden University)H-Index: 1
#2Dominik Witzigmann (UBC: University of British Columbia)H-Index: 16
Last. Daan J.A. Crommelin (UU: Utrecht University)H-Index: 90
view all 7 authors...
Abstract A drawback of the current mRNA-lipid nanoparticle (LNP) COVID-19 vaccines is that they have to be stored at (ultra)low temperatures. Understanding the root cause of the instability of these vaccines may help to rationally improve mRNA-LNP product stability and thereby ease the temperature conditions for storage. In this review we discuss proposed structures of mRNA-LNPs, factors that impact mRNA-LNP stability and strategies to optimize mRNA-LNP product stability. Analysis of mRNA-LNP st...
2 CitationsSource
#1Qurrat Ul Ain (UBC: University of British Columbia)H-Index: 1
#1Qurrat Ul Ain (UBC: University of British Columbia)H-Index: 1
Last. Sarah Hedtrich (UBC: University of British Columbia)H-Index: 21
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Gene therapies are powerful tools to prevent, treat, and cure human diseases. The application of gene therapies for skin diseases received little attention so far, despite the easy accessibility of skin and the urgent medical need. A major obstacle is the unique barrier properties of human skin, which significantly limits the absorption of biomacromolecules, and thus hampers the efficient delivery of nucleic acid payloads. In this review, we discuss current approaches, successes, and failures of...
1 CitationsSource
#1Nisha Chander (UBC: University of British Columbia)
#2Johannes Morstein (NYU: New York University)H-Index: 9
Last. Dominik Witzigmann (UBC: University of British Columbia)H-Index: 16
view all 7 authors...
Encapsulation of small molecule drugs in long-circulating lipid nanoparticles (LNPs) can reduce toxic side effects and enhance accumulation at tumor sites. A fundamental problem, however, is the slow release of encapsulated drugs from these liposomal systems at the disease site resulting in limited therapeutic benefit. Methods to trigger release at specific sites are highly warranted. Here, it is demonstrated that incorporation of ultraviolet (UV-A) or red-light photoswitchable-phosphatidylcholi...
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#1Anna Pratsinis (University of Basel)
#2Philipp Uhl (University Hospital Heidelberg)H-Index: 7
Last. Jörg Huwyler (University of Basel)H-Index: 49
view all 9 authors...
Recently, a lipopeptide derived from the hepatitis B virus (HBV) large surface protein has been developed as an HBV entry inhibitor. This lipopeptide, called MyrcludexB (MyrB), selectively binds to the sodium taurocholate cotransporting polypeptide (NTCP) on the basolateral membrane of hepatocytes. Here, the feasibility of coupling therapeutic enzymes to MyrB was investigated for the development of enzyme delivery strategies. Hepatotropic targeting shall enable enzyme prodrug therapies and detox...
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#1Kent Chen (BC Cancer Research Centre)H-Index: 4
#2Gardenia G C Militao (UFPE: Federal University of Pernambuco)H-Index: 1
Last. Marcel B. BallyH-Index: 80
view all 6 authors...
Abstract For more than 30 years, treatment of acute myeloid leukemia (AML) has remained largely unchanged and reliant on chemotherapeutic drug combinations, specifically cytarabine and daunorubicin (the 7 + 3 regimen). One broad spectrum drug, flavopiridol (also known as Alvocidib) has shown significant activity against AML through the inhibition of cyclin-dependent kinases. Flavopiridol is a semisynthetic flavonoid and our research team recently described methods to formulate another flavonoid,...
1 CitationsSource