{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:12:42Z","timestamp":1792177962053,"version":"4.4.0"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Research Council of Finland, GeneCellNano Flagship","doi-asserted-by":"publisher","award":["319187"],"award-info":[{"award-number":["319187"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AFM Telethon foundation","award":["23716"],"award-info":[{"award-number":["23716"]}]},{"DOI":"10.13039\/501100003125","name":"Finnish Cultural Foundation","doi-asserted-by":"publisher","award":["35251305"],"award-info":[{"award-number":["35251305"]}],"id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010129","name":"Maud Kuistila Memorial Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010129","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Lentiviral vectors (LVs) are most commonly pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G), which lends LVs a wide tropism as it uses the low-density lipoprotein receptor (LDLR) as the main receptor for cell entry. In some gene therapy and research applications, however, alternative pseudotypes can be useful. In this work, we characterized LVs pseudotyped with lymphocytic choriomeningitis virus (LCMV) glycoprotein, particularly in gene transfer to an LDLR-deficient mouse strain used to model cardiovascular disease, Ldlr\u2212\/\u2212ApoB100\/100. Methods: LCMV-LVs were used in vitro to test their transduction efficiency across a variety of cell types. In vivo, the gene transfer efficiency, LV-specific immune responses and biodistribution of VSV-G-LVs and LCMV-LVs were compared after systemic gene transfer. Results: In vitro, LCMV-LVs transduced all tested cell types at high efficiency without the use of transduction enhancers. In vivo, VSV-G-LVs showed a higher gene transfer efficiency at the same LV dose, but increasing the LCMV-LV dose enhanced the measured vector copy numbers. With both pseudotypes, most of the vector accrued in the liver, but with LCMV-LVs, a larger portion of the measured vector copies were found in the lungs. VSV-G-LVs also generated a higher titer of LV-specific IgG antibodies. The gene transfer efficiency of LCMV-LVs was affected by the mouse diet, with a high-fat diet decreasing the transduction. Conclusions: LCMV-LVs can be used as a substitute for VSV-G-LVs if an alternative pseudotype is required; however, they may require the use of a higher LV dose.<\/jats:p>","DOI":"10.3390\/genes17010060","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:28:57Z","timestamp":1767626937000},"page":"60","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficiency of Lentiviral Vectors Pseudotyped with LCMV-G in Gene Transfer to Ldlr\u2212\/\u2212ApoB100\/100 Mice"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2570-8454","authenticated-orcid":false,"given":"Alisa","family":"Nousiainen","sequence":"first","affiliation":[{"name":"A. I. Virtanen Institutefor Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8512-3768","authenticated-orcid":false,"given":"Anna-Kaisa","family":"Ruotsalainen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institutefor Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Hokkanen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institutefor Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Laidinen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institutefor Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Tawfek","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institutefor Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8854-8585","authenticated-orcid":false,"given":"Diana","family":"Schenkwein","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institutefor Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7593-2708","authenticated-orcid":false,"given":"Seppo","family":"Yl\u00e4-Herttuala","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institutefor Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland"},{"name":"Heart Center and Gene Therapy Unit, Kuopio University Hospital, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1042\/BJ20120146","article-title":"Lentiviral vectors: Basic to translational","volume":"443","author":"Sakuma","year":"2012","journal-title":"Biochem J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8463","DOI":"10.1128\/JVI.72.11.8463-8471.1998","article-title":"A Third-Generation Lentivirus Vector with a Conditional Packaging System","volume":"72","author":"Dull","year":"1998","journal-title":"J. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8150","DOI":"10.1128\/JVI.72.10.8150-8157.1998","article-title":"Development of a Self-Inactivating Lentivirus Vector","volume":"72","author":"Miyoshi","year":"1998","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5270","DOI":"10.1128\/jvi.64.11.5270-5276.1990","article-title":"Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity","volume":"64","author":"Page","year":"1990","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/nbt0997-871","article-title":"Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo","volume":"15","author":"Zufferey","year":"1997","journal-title":"Nat. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/s41467-018-03432-4","article-title":"Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein","volume":"9","author":"Nikolic","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7306","DOI":"10.1073\/pnas.1214441110","article-title":"LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus","volume":"110","author":"Finkelshtein","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1182\/blood-2014-02-558163","article-title":"Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs","volume":"124","author":"Amirache","year":"2014","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1182\/bloodadvances.2018027508","article-title":"Baboon envelope LVs efficiently transduced human adult, fetal, and progenitor T cells and corrected SCID-X1 T-cell deficiency","volume":"3","author":"Bernadin","year":"2019","journal-title":"Blood Adv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1128\/JVI.02032-12","article-title":"Nipah Virus Envelope-Pseudotyped Lentiviruses Efficiently Target ephrinB2-Positive Stem Cell Populations In Vitro and Bypass the Liver Sink When Administered In Vivo","volume":"87","author":"Palomares","year":"2013","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1089\/hum.2020.127","article-title":"In Vivo Gene Therapy for Canine SCID-X1 Using Cocal-Pseudotyped Lentiviral Vector","volume":"32","author":"Rajawat","year":"2021","journal-title":"Hum. Gene Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"114689","DOI":"10.1016\/j.jviromet.2023.114689","article-title":"Protocol for a high titer of BaEV-Rless pseudotyped lentiviral vector: Focus on syncytium formation and detachment","volume":"314","author":"Noguchi","year":"2023","journal-title":"J. Virol. Methods"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pasquato, A., Cendron, L., and Kunz, S. (2018). Cleavage of the glycoprotein of arenaviruses. Activation of Viruses by Host Proteases, Springer International Publishing.","DOI":"10.1007\/978-3-319-75474-1_3"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1479-0556-9-8","article-title":"Altering \u03b1-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism","volume":"9","author":"Dylla","year":"2011","journal-title":"Genet. Vaccines Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1292\/jvms.12-0176","article-title":"Cell surface molecules involved in infection mediated by lymphocytic choriomeningitis virus glycoprotein","volume":"74","author":"Shimojima","year":"2012","journal-title":"J. Vet. Med. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1128\/JVI.76.3.1488-1495.2002","article-title":"Oncoretrovirus and Lentivirus Vectors Pseudotyped with Lymphocytic Choriomeningitis Virus Glycoprotein: Generation, Concentration, and Broad Host Range","volume":"76","author":"Beyer","year":"2002","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1089\/hgtb.2014.105","article-title":"Pseudotyping Lentiviral Vectors with Lymphocytic Choriomeningitis Virus Glycoproteins for Transduction of Dendritic Cells and In Vivo Immunization","volume":"25","author":"Zhang","year":"2014","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1089\/104303403769211691","article-title":"Correction of Bleeding Diathesis Without Liver Toxicity Using Arenaviral-Pseudotyped HIV-1-Based Vectors in Hemophilia A Mice","volume":"14","author":"Park","year":"2003","journal-title":"Hum. Gene Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1172\/JCI4164","article-title":"Lipoprotein clearance mechanisms in LDL receptor-deficient \u201capo-B48- only\u201d and \u201capo-B100-only\u201d mice","volume":"102","author":"Zlot","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1093\/cvr\/cvt148","article-title":"The effects of VEGF-A on atherosclerosis, lipoprotein profile, and lipoprotein lipase in hyperlipidaemic mouse models","volume":"99","author":"Heinonen","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41598-017-00376-5","article-title":"High Plasma Lipid Levels Reduce Efficacy of Adenovirus-Mediated Gene Therapy","volume":"7","author":"Huusko","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hu, P., Hao, Y., Tang, W., Diering, G.H., Zou, F., and Kafri, T. (2025). Analysis of Hepatic Lentiviral Vector Transduction: Implications for Preclinical Studies and Clinical Gene Therapy Protocols. Viruses, 17.","DOI":"10.3390\/v17020276"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/S0076-6879(02)46071-5","article-title":"Generation of HIV-1 derived lentiviral vectors","volume":"346","author":"Follenzi","year":"2002","journal-title":"Methods Enzymol."},{"key":"ref_24","first-page":"35","article-title":"How to calculate sample size in animal studies?","volume":"1","author":"Shah","year":"2011","journal-title":"Natl. J. Physiol. Pharm. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"115106","DOI":"10.1016\/j.jviromet.2024.115106","article-title":"Improving the production of BaEV lentivirus by comprehensive optimization","volume":"333","author":"Li","year":"2025","journal-title":"J. Virol. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1017\/S0950268805005431","article-title":"Hantavirus and arenavirus antibody prevalence in rodents and humans in Trentino, Northern Italy","volume":"134","author":"Laakkonen","year":"2006","journal-title":"Epidemiol. Infect."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Vilibic-Cavlek, T., Oreski, T., Korva, M., Kolaric, B., Stevanovic, V., Zidovec-Lepej, S., Tabain, I., Jelicic, P., Miklausic-Pavic, B., and Savic, V. (2021). Prevalence and Risk Factors for Lymphocytic Choriomeningitis Virus Infection in Continental Croatian Regions. Trop. Med. Infect. Dis., 6.","DOI":"10.3390\/tropicalmed6020067"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.1002\/j.1460-2075.1988.tb03306.x","article-title":"Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor","volume":"7","author":"Herz","year":"1988","journal-title":"EMBO J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1152\/physrev.00033.2007","article-title":"LDL receptor-related protein 1: Unique tissue-specific functions revealed by selective gene knockout studies","volume":"88","author":"Lillis","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1006\/mthe.2002.0630","article-title":"Biodistribution and Toxicity Studies of VSVG-Pseudotyped Lentiviral Vector after Intravenous Administration in Mice with the Observation of in Vivo Transduction of Bone Marrow","volume":"6","author":"Pan","year":"2002","journal-title":"Mol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1182\/blood-2006-11-059873","article-title":"The immune response to lentiviral-delivered transgene is modulated in vivo by transgene-expressing antigen-presenting cells but not by CD4+CD25+ regulatory T cells","volume":"110","author":"Annoni","year":"2007","journal-title":"Blood"},{"key":"ref_32","unstructured":"Unemo, M., Cole, M., Lewis, D., Ndowa, F., Van Der Pol, B., and Wi, T. (2023). Laboratory and Point-of-Care Diagnostic Testing for Sexually Transmitted Infections, Including HIV, World Health Organization."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ymthe.2020.01.001","article-title":"Immune Responses to Viral Gene Therapy Vectors","volume":"28","author":"Shirley","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11650","DOI":"10.1128\/JVI.00955-07","article-title":"Early Antibodies Specific for the Neutralizing Epitope on the Receptor Binding Subunit of the Lymphocytic Choriomeningitis Virus Glycoprotein Fail To Neutralize the Virus","volume":"81","author":"Eschli","year":"2007","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/ni1102","article-title":"Deliberate removal of T cell help improves virus-neutralizing antibody production","volume":"5","author":"Recher","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8686","DOI":"10.1126\/sciimmunol.aam8686","article-title":"Sustained T follicular helper cell response is essential for control of chronic viral infection","volume":"2","author":"Greczmiel","year":"2017","journal-title":"Sci. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1002\/eji.201343565","article-title":"Nucleoprotein-specific nonneutralizing antibodies speed up LCMV elimination independently of complement and Fc\u03b3R","volume":"43","author":"Straub","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1093\/intimm\/9.11.1757","article-title":"Cooperation of B cells and T cells is required for survival of mice infected with vesicular stomatitis virus","volume":"9","author":"Thomsen","year":"1997","journal-title":"Int. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1182\/blood-2006-10-049312","article-title":"In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance","volume":"109","author":"Brown","year":"2007","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1161\/ATVBAHA.111.237693","article-title":"Animal Models of Atherosclerosis","volume":"32","author":"Getz","year":"2012","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nm1398","article-title":"Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer","volume":"12","author":"Brown","year":"2006","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7325","DOI":"10.1126\/scitranslmed.aav7325","article-title":"Phagocytosis-shielded lentiviral vectors improve liver gene therapy in nonhuman primates","volume":"11","author":"Milani","year":"2019","journal-title":"Sci. Transl. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/1\/60\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T05:24:52Z","timestamp":1767763492000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/1\/60"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["genes17010060"],"URL":"https:\/\/doi.org\/10.3390\/genes17010060","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]}}}