A targeted controlled force injection of genetic material in vivo
A general limitation in gene delivery is the cellular uptake in lager animals including humans. Several approaches have been tested including liposomes, micro-needles, in vivo electro-transfer, ballistic delivery, and needle-free delivery. All these techniques have individual limitations. One approa...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-01-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050116301577 |
| _version_ | 1819295053755973632 |
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| author | Gustaf Ahlén Lars Frelin Fredrik Höolmstrm Grant Smetham Steve Augustyn Matti Sällberg |
| author_facet | Gustaf Ahlén Lars Frelin Fredrik Höolmstrm Grant Smetham Steve Augustyn Matti Sällberg |
| author_sort | Gustaf Ahlén |
| collection | DOAJ |
| description | A general limitation in gene delivery is the cellular uptake in lager animals including humans. Several approaches have been tested including liposomes, micro-needles, in vivo electro-transfer, ballistic delivery, and needle-free delivery. All these techniques have individual limitations. One approach reproducibly delivering genetic material in muscle tissue in nonhuman primates is hydrodynamic injection, a forced injection of a volume equaling the volume of the tissue to be transfected thereby causing an increased local pressure resulting in an improved uptake of genetic material. We transferred the principle of hydrodynamic injection to a device, where a small injection volume can be delivered to a targeted tissue volume, termed in vivo intracellular injection (IVIN). The device is based on needle(s) with apertures along the needle shafts, where multiple needles can fix the tissue volume to be transfected. The apertures direct the injection from a central needle outward or inward to the centroid of a geometric arrangement thereby targeting the tissue to be transfected. With a controlled force, this results in a targeted injection with increased transfection efficiency. We here show that the IVIN technology reproducibly improved plasmid uptake and expression and the immunogenicity. The IVIN technology can be generally applied to a targeted delivery of genetic materials. |
| first_indexed | 2024-12-24T04:36:06Z |
| format | Article |
| id | doaj.art-dcbf41bca41945d3b08bfecd864e56a1 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-24T04:36:06Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-dcbf41bca41945d3b08bfecd864e56a12022-12-21T17:15:12ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012016-01-013C10.1038/mtm.2016.16A targeted controlled force injection of genetic material in vivoGustaf Ahlén0Lars Frelin1Fredrik Höolmstrm2Grant Smetham3Steve Augustyn4Matti Sällberg5Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, SwedenDepartment of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, SwedenDepartment of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, SwedenTeam Consulting Limited, Cambridge, UKTeam Consulting Limited, Cambridge, UKDepartment of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, SwedenA general limitation in gene delivery is the cellular uptake in lager animals including humans. Several approaches have been tested including liposomes, micro-needles, in vivo electro-transfer, ballistic delivery, and needle-free delivery. All these techniques have individual limitations. One approach reproducibly delivering genetic material in muscle tissue in nonhuman primates is hydrodynamic injection, a forced injection of a volume equaling the volume of the tissue to be transfected thereby causing an increased local pressure resulting in an improved uptake of genetic material. We transferred the principle of hydrodynamic injection to a device, where a small injection volume can be delivered to a targeted tissue volume, termed in vivo intracellular injection (IVIN). The device is based on needle(s) with apertures along the needle shafts, where multiple needles can fix the tissue volume to be transfected. The apertures direct the injection from a central needle outward or inward to the centroid of a geometric arrangement thereby targeting the tissue to be transfected. With a controlled force, this results in a targeted injection with increased transfection efficiency. We here show that the IVIN technology reproducibly improved plasmid uptake and expression and the immunogenicity. The IVIN technology can be generally applied to a targeted delivery of genetic materials.http://www.sciencedirect.com/science/article/pii/S2329050116301577 |
| spellingShingle | Gustaf Ahlén Lars Frelin Fredrik Höolmstrm Grant Smetham Steve Augustyn Matti Sällberg A targeted controlled force injection of genetic material in vivo Molecular Therapy: Methods & Clinical Development |
| title | A targeted controlled force injection of genetic material in vivo |
| title_full | A targeted controlled force injection of genetic material in vivo |
| title_fullStr | A targeted controlled force injection of genetic material in vivo |
| title_full_unstemmed | A targeted controlled force injection of genetic material in vivo |
| title_short | A targeted controlled force injection of genetic material in vivo |
| title_sort | targeted controlled force injection of genetic material in vivo |
| url | http://www.sciencedirect.com/science/article/pii/S2329050116301577 |
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