hybrid vectors
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2021 ◽  
Vol 41 ◽  
pp. 245-268
Author(s):  
TK Brenner ◽  
◽  
K Posa-Markaryan ◽  
D Hercher ◽  
S Sperger ◽  
...  

Reconstruction of bone defects and compensation of deficient repair mechanisms represent important goals within the field of regenerative medicine and require novel safe strategies for translation into the clinic. A non-viral osteogenic gene therapeutic vector system (‘hybrid vectors’) was generated, combining an improved bone morphogenetic protein 2 (BMP2) gene cassette and single pro-osteogenic microRNAs (miR-148b-3p, miR-20-5p, miR-590b-5p), driven by the U6 promoter. The vectors were tested in vitro for their osteogenic differentiation potential in C2C12 and C3H/10T1/2 cell lines, using BMP2 alone as control. After confirming BMP2 expression and miRNA transcription, increased osteogenic differentiation was observed by all hybrid vectors, but most consistently by BMP2/miR-590-5p, using alkaline phosphatase enzyme activity assays and osteogenic marker mRNA quantitation, including runt-related transcription factor 2 (Runx2), collagen type 1 (Col1a1) and osteocalcin. To visualise target mRNAs of the respective miRNAs, next generation sequencing was performed, confirming down-regulation of mRNA targets of the hybrid vectors. Since the hybrid vector consisting of BMP2 and miR-590-5p showed the largest increase in osteogenic differentiation in vitro, this was tested in a mouse ectopic-bone model. Mineralisation was more than with BMP2 alone. The present study showed hybrid vectors as a novel non-viral gene therapeutic plasmid system for combining therapeutic effects of recombinant protein expression and miRNA transcription that did not add to the burden of the translation machinery, while improving the therapeutic efficacies. In vivo proof-of-principle in the context of bone regeneration suggested that such hybrid vectors will be applicable in a wide array of gene therapeutic strategies.



2021 ◽  
Author(s):  
Lourdes Mónica Bravo-Anaya ◽  
Julien Rosselgong ◽  
Karla Gricelda Fernández-Solís ◽  
Ye Xiao ◽  
Amélie Vax ◽  
...  

Hybrid cationic ELPs for nucleic acids transport and delivery were synthetized through the coupling of RAFT polymerization and biorthogonal chemistry of ELPs, introducing a specific number of positive charges to the ELP backbone.



Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 239
Author(s):  
Takuya Hashimoto ◽  
Tomoya Hirata ◽  
Eiji Yuba ◽  
Atsushi Harada ◽  
Kenji Kono

Background: Gene delivery to target cells is crucially important to establish gene therapy and regenerative medicine. Although various virus-based and synthetic molecule-based gene vectors have been developed to date, selective transfection in a site or a cell level is still challenging. For this study, both light-responsive and temperature-responsive synthetic gene vectors were designed for spatiotemporal control of a transfection system. Methods: 11-Mercaptoundecanoic acid-coated gold nanorods were mixed with polyamidoamine dendron-bearing lipids of two types having amino-terminus or ethoxydiethylene glycol-terminus to obtain hybrid vectors. Hybrid vectors were mixed further with pDNA. Then we investigated their physicochemical properties and transfection efficacy with or without near infrared laser irradiation. Results: Hybrid vectors formed complexes with pDNA and exhibited enhanced photothermal property under near infrared laser irradiation compared with parent gold nanorods. Transfection efficacy of complexes was promoted considerably by brief laser irradiation soon after complex application to the cells. Analysis of intracellular distribution revealed that laser irradiation promoted the adsorption of complexes to the cells and cytosolic release of pDNA, which is derived from the change in surface hydrophobicity of complexes through dehydration of temperature-responsive groups. Conclusions: Hybrid vector is promising as a light-activatable transfection system.



2020 ◽  
Vol 23 (2) ◽  
Author(s):  
Sravanthi Vupputuri ◽  
Lobat Tayebi ◽  
Rangika S. Hikkaduwa Koralege ◽  
Adane Nigatu ◽  
Masoud Mozafari ◽  
...  


2019 ◽  
Vol 37 (11) ◽  
pp. 1302-1313 ◽  
Author(s):  
Lupeng Ye ◽  
Jonathan J. Park ◽  
Matthew B. Dong ◽  
Quanjun Yang ◽  
Ryan D. Chow ◽  
...  


2019 ◽  
Vol 134 ◽  
pp. 1002-1012 ◽  
Author(s):  
Menglu Xu ◽  
Sajid Asghar ◽  
Shuang Dai ◽  
Yajing Wang ◽  
Shanshan Feng ◽  
...  


Polymers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 243 ◽  
Author(s):  
Shashank Pinnapireddy ◽  
Mohamed Raafat El Assy ◽  
Patrick Schlote ◽  
Udo Bakowsky

The major obstacle facing efficient gene therapy is the development of reliable delivery vehicles, which are both nontoxic and biocompatible and possess efficient cell-specific gene delivery. Previously, hybrid delivery vehicles comprising anionic liposomes and cationic polymers have been used successfully for gene therapy. In this study, hybrid vectors based on glycosylated artificial viral envelopes (including two novel compositions mimicking HIV and HSV envelopes) and polyethylenimine were morphologically and physiologically characterised. Transfection studies showed that the hybrid vectors based on the control liposomes, and their glycosylated modifications, had significantly higher transfection rates compared to the polyplexes. Improvement in the transfection efficiency was observed with the glycosylated HIV- and HSV-mimicking hybrid vectors, which also showed a safe biocompatibility profile based on the cytotoxicity and haemocompatibility assays. These glycosylated artificial viral envelope-based hybrid vectors could be used as safe gene delivery systems with potential to become new compositions for efficient nonviral gene therapy.



MedChemComm ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 1692-1718 ◽  
Author(s):  
A. Gigante ◽  
M. Li ◽  
S. Junghänel ◽  
C. Hirschhäuser ◽  
S. Knauer ◽  
...  

Hybrid vectors are a remarkable strategy to address the current challenges in gene delivery.



BioTechniques ◽  
2018 ◽  
Vol 64 (5) ◽  
pp. 219-224 ◽  
Author(s):  
Deshui Yu ◽  
Libing Liao ◽  
Ju Zhang ◽  
Yi Zhang ◽  
Kedong Xu ◽  
...  


Author(s):  
Manohar Mahato ◽  
Giridhara R. Jayandharan ◽  
Praveen Kumar Vemula
Keyword(s):  


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