Gene transfer techniques are an important tool in studies of gene function as well as in the clinical evaluation of new treatments. In research the most important impact of efficient transient and stable gene transfer methods is the generation of new cell lines or animal models for the basic research of protein functions. Many of these methods are based on utilization of viruses as means to target and deliver genes into appropriate cells. In addition, recent advances in the CRISPR-methodology enable the same delivery method to be used to efficiently edit specific genes in cells.

Successful work with sophisticated viral methods requires special expertise and strict safety considerations both of which are found at all of the Biocenters in Finland. VGTCT brings together all significant players in the field of viral vectors and gene transfer technologies in Finland. It has established a well-functioning collaborative network that serves Finnish research community with validated vectors which can be obtained in a reasonable price and waiting time. VGTCT exploits synergies between different Biocenters by recognizing their different expertise and research profiles and avoids duplications of unnecessary overlapping work within the network.


Nodes


Node/Host UniversityNode PI
National Virus Vector Core Laboratory (NVVL), UEF
Professor Seppo Ylä-Herttuala, UEF, seppo.ylaherttuala@uef.fi
AAV Core (AAV Gene Transfer and Cell Therapy Core Facility), UH
Professor Taija Mäkinen, UH
taija.makinen@helsinki.fi
Biomedicum Virus Core (HelVi-BVC), UH
Professor Juha Klefström, UH
juha.klefstrom@helsinki.fi
Biocenter Oulu Virus Core Laboratory, UO
Professor Aki Manninen, UO
aki.manninen@oulu.fi
Tampere Virus Core Facility (TVCF), TAU
Senior Research Fellow Eric Dufour, TAU
eric.dufour@tuni.fi
Genome Editing Core, ÅAU, UTU
Senior Research Fellow Eleanor Coffey ÅAU/ UTU
ecoffey@abo.fi
Virus and imaging facility, JYU
Docent Maija Vihinen-Ranta, JYU
maija.vihinen-ranta@jyu.fi

UEF: University of Eastern Finland; UH: University of Helsinki; UO: University
of Oulu; UTU: University of Turku; TAU: Tampere University; ÅAU: Åbo
Akademi University.



Contact details


Platform Chair
Seppo Ylä-Herttuala, seppo.ylaherttuala@uef.fi



Services


National Virus Vector Laboratory (NVVL)


National Virus Vector Laboratory (NVVL) focuses on larger scale, highly purified vector production with disposable bioreactors and high-capacity downstream purification of the vectors. GMP-trained personnel and methods will also be very important for the projects when they move closer to clinical applications, thus avoiding costly duplication of the early work if it does not meet minimum criteria required for regulatory agencies.

Services:
  • Midi (0.5 ml) and large scale (>5 ml) production of highly purified, high titer adenovirus, lentivirus and AAV vectors
  • Base & Prime editing and gRNA vectors
  • Lentivectors for CAR-T cell production
  • Bioreactor productions
  • Validated titration of virus preps
  • Validated sterility, lipopolysaccharide and mycoplasma QC assays
  • Training courses of researchers for in vitro and in vivo animal gene transfer methods

The University of Helsinki Viral Cores (HelVi)


The University of Helsinki Viral Cores (HelVi) consists of two integrated units: the AAV Core and the Biomedicum Virus Core (BVC).
 
The AAV Core is a service platform that specializes in the generation of recombinant adeno-associated viral (rAAV) vectors for academic and industrial customers.

Services:
  • Manufacturing recombinant AAV (rAAV) preps of four different serotypes (AAV2, AAV6, AAV8, AAV9) from the custom-modified gene-encoding vector plasmids
  • Routine viral particle quantification protocol and functional tests of the rAAV preps to characterize viral particle concentration, transduction efficiency and protein production by the recombinant vector
  • Providing consultation to customers regarding rAAV vector design, tissue/cell specificity of transduction, gene silencing (or inactivation via Crispr/Cas9) and fluorescent markers
  • Generation of CRISPR rAAV preps for genome editing in both mice and cultured cells
HelVi-BVC manufactures and produces lenti- and retrovirus particles from customer plasmids using optimised methods to produce high-quality viral particles. We also provide BSL-2 working lab space for preparation of RV and LV vectors. We offer all services for internal (UH) and Biocenter Finland network customers, but also for external customers (companies, institutes, and universities).Services:
  • A “researcher hotel” i.e. a BSL-2 facility for recombinant virus work for all customers who do not have other access to a BSL-2 space.
  • Biosafety training for anyone willing to work in the BSL-2 facility.
  • Lentiviral p24 titre testing and testing transduced cells for replicating competent viruses (RCV testing).
  • Customer service and support; we help our customers with recombinant virus-related questions, help them to plan their projects or to apply for GMO permits

Oulu Virus Core Facility


Oulu Virus Core Facility provides regular small-scale virus production services. Core personnel also assist in design of viral CRISPR-knockout, CRISPR-knockin and RNAi-knockdown tools to generate cell lines. Core also hosts Lyncee Tech digital holographic microscopy setup and 10XGenomics Chromium cell partitioning system. A particular focus has been on the development of analysis platforms for virally transduced 3D cell culture models including patient-derived organoid cultures, developed together with the BCO Structural Biology Core equipped with high throughput pipetting and screening setups suitable for Drug Sensitivity and Resistance Testing (DSRT).

Services:
  • Mini scale (100 µl) production of adenoviruses and lentiviruses
  • Trouble-shooting and special advice in making and testing CRISPR/Cas9- and RNAi-vectors
  • Production of lentiviruses for the generation of transgenic and knock-down mice
  • Holographic microscopy of virally transduced cells
  • Provides a fully equipped lab for researchers wishing to work with their own vectors

Tampere Virus Core Facility (TVCF)


Tampere Virus Core Facility (TVCF) provides local researchers and their national/international collaborators with state-of-the-art lenti/retro/sendai virus production, cell transduction and certification services. TVCF is specialized in supporting iPSc, stem-cell and differentiated cell work. TVCF recently integrated live-enterovirus work and services for live-HSV1 viruses. TVCF also recently expanded its support for BSL-2 bioenergetics (XF24 instrument) work. Services include planning, design, troubleshooting and practical support for viral work. TVCF offers cherry-pickable libraries of human lenti-gRNAs (1000 targets, 3-4 guide per targets), and Cas9 vectors. TVCF provides fully maintained and equipped laboratory space for virus work in Tampere University on an hourly based price.

Services:
  • Mini scale (100 µl) lentivirus and retrovirus production and cell transduction service
  • Live enteroviral and HSV1 studies
  • Bioenergetic measurements
  • Lentivirus /retrovirus free cell lines certification
  • Common facility for virus work based on an hourly rate

The Turku Core


The Turku Core provides services including viral vector production (retroviruses, lenti, AAVs) and vector titration (viral genome count QPCR, retrovirus RCV test) as a service, as well as genome editing services. Providing biosafety support services has become a much-appreciated part of our services. We help users to carry out their GMO risk assessments for viral use. Finally, we provide a fully supported BSL-2 laboratory for safe work with viruses.

Services:
  • Mini scale (100 µl) production of adeno, LV and AAV mainly for in vitro use
  • Titration of virus preparations
  • CRISPR genome editing vectors and shRNA knockdown constructs
  • Safety training and consultation
  • Provides a fully equipped lab for researchers wishing to work with their own vectors

JYU


JYU provides laboratory equipped with Leica TCS SP8X Falcon white laser confocal microscope with Phasor FLIM analysis tool, Nikon A1R laser scanning confocal microscope, JEOL JEM-1400HC Transmission Electron Microscope (TEM), Bruker Quantax400 EDS (Zeiss EVO-50XVP) Scanning Electron Microscope (SEM), Nanomics Scanning Near-field optical Microscope (SNOM), and Bruker Quantax 400 ED Dispensive Raman Microscope. Facilities for Correlative light and electron microscopy CLEM. Access to Serial block face scanning electron microscopy (SBF-SEM) and Focused Ion Beam Scanning Electron Microscopy FIB-SEM. Moreover, the microinjector combined with a fluorescent microscope and the comet assay (single-cell gel electrophoresis) for measuring deoxyribonucleic acid (DNA) strand breaks are in use. The access is mostly based on collaboration with the PI or other research group leaders in JYU and other Biocenter universities.

Services:
  • Virus live microscopy
  • Electron microscopy of viral vectors

Recent user publications


Mushimiyimana I, Niskanen H, Beter M, Laakkonen JP, Kaikkonen MU, Ylä-Herttuala S, and Laham-Karam N. 2021. “Characterization of a Functional Endothelial Super-Enhancer That Regulates ADAMTS18 and Angiogenesis.” Nucleic Acids Research 49 (14): 8078–96. doi: 10.1093/nar/gkab633.

Freitag TL, Fagerlund R, Karam NL, Leppänen VM, Ugurlu H, Kant R, Mäkinen P, Tawfek A, Jha SK, Strandin T, Leskinen K, Hepojoki J, Kesti T, Kareinen L, Kuivanen S, Koivulehto E, Sormunen A, Laidinen S, Khattab A, Saavalainen P, Meri S, Kipar A, Sironen T, Vapalahti O, Alitalo K, Ylä-Herttuala S, Saksela K. 2023. “Intranasal Administration of Adenoviral Vaccines Expressing SARS-CoV-2 Spike Protein Improves Vaccine Immunity in Mouse Models.” Vaccine 41 (20): 3233–46. doi: 10.1016/j.vaccine.2023.04.020.

Grunewald M, Kumar S, Sharife H, Volinsky E, Gileles-Hillel A, Licht T, Permyakova A, Hinden L, Azar S, Friedmann Y, Kupetz P, Tzuberi R, Anisimov A, Alitalo K, Horwitz M, Leebhoff S, Khoma OZ, Hlushchuk R, Djonov V, Abramovitch R, Tam J, Keshet E. 2021. “Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span.” Science. Jul 30;373(6554):eabc8479. doi: 10.1126/science.abc8479.

Merlini A, Haberl M, Strauß J, Hildebrand L, Genc N, Franz J, Chilov D, Alitalo K, Flügel-Koch C, Stadelmann C, Flügel A, and Odoardi F. 2022. “Distinct Roles of the Meningeal Layers in CNS Autoimmunity.” Nature Neuroscience 25 (7): 887–99. doi: 10.1038/s41593-022-01108-3.

Pavic K, Gupta N, Omella JD, Derua R, Aakula A, Huhtaniemi R, Määttä JA, Höfflin N, Okkeri J, Wang Z, Kauko O, Varjus R, Honkanen H, Abankwa D, Köhn M, Hytönen VP, Xu W, Nilsson J, Page R, Janssens V, Leitner A, Westermarck J. 2023. ”Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A.” Nat Commun. Feb 28;14(1):1143. doi: 10.1038/s41467-023-36693-9.


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