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At least 73 records · Page 4Linked to original sources
PubMed2017

Systemic and Persistent Muscle Gene Expression in Rhesus Monkeys with a Liver De-Targeted Adeno-Associated Virus Vector.

The liver is a major off-target organ in gene therapy approaches for cardiac and musculoskeletal disorders. Intravenous administration of most of the naturally occurring adeno-associated virus (AAV) strains invariably results in vector genome sequestration within the liver. In the current study, we compared the muscle tropism and transduction efficiency of a liver de-targeted AAV variant to AAV9 following systemic administration in newborn rhesus monkeys. In vivo bioluminescence imaging was performed to monitor transgene expression (firefly luciferase) post administration. Results indicated comparable and sustained levels of systemic firefly luciferase gene expression in skeletal muscle over a period of two years. Quantitation of vector biodistribution in harvested tissues post-administration revealed widespread recovery of vector genomes delivered by AAV9 but markedly decreased levels in major systemic organs from the AAV variant. These studies validate the translational potential and safety of liver de-targeted AAV strains for gene therapy of muscle-related diseases.

Animals↗
PubMed2026

A randomized trial of viral vector and adjuvanted protein HBV therapeutic vaccine in people with chronic hepatitis B on nucleos(t)ide analogs.

BACKGROUND: This study assessed the safety, efficacy, and immunogenicity of a therapeutic immunization strategy aimed at reaching a functional cure for chronic hepatitis B (CHB), relying on a heterologous prime-boost with viral vectors ChAd155-hIi-HBV and MVA-HBV, combined with sequential or concomitant administration of adjuvanted recombinant HBV proteins (HBc-HBs/AS01B). METHODS: This single-blind, randomized, controlled, first-in-human, phase 1/2 trial enrolled adults aged 18-65 years with HBeAg-negative CHB, virally suppressed on nucleos(t)ide analogs (NAs), with HBsAg >50 IU/mL. Participants received NAs and the following regimens of 4 doses (8-week intervals): sequential administration of ChAd155-hIi-HBV, MVA-HBV, and 2 HBc-HBs/AS01B doses; co-administration of ChAd155-hIi-HBV+HBc-HBs/AS01B, followed by 3 co-administered MVA-HBV+HBc-HBs/AS01B doses; 4 HBc-HBs/AS01B doses; 2 placebo doses followed by ChAd155-hIi-HBV and MVA-HBV administered alone or with HBc-HBs/AS01B; or 4 placebo doses. Safety, efficacy (≥1-log decrease in quantitative (q)HBsAg or HBsAg loss 24 weeks post-dose 4 [day (D)337]), antibody, and T-cell responses were evaluated. RESULTS: In all, 134 participants were vaccinated. Grade 3 solicited adverse events (AEs) (median duration: 2-3 days) were more frequent after co-administration (systemic: 59.3%; administration-site: 33.3%) than sequential administration (systemic: 10.3%; administration-site: 12.8%) of high-dose viral vectors and proteins. No vaccine-related or fatal serious AEs were reported. After 4 doses, no participant had HBsAg loss or ≥1-log decrease in qHBsAg (D337 vs. D1). Co-administration induced the strongest anti-HBs response (73.7% achieved anti-HBs ≥10 mIU/mL 2 weeks post-dose 4 vs. 40.0% after sequential administration). Both sequential and co-administration induced HBc-specific CD4+ and CD8+ T-cell responses, with a prime-boost effect of the viral vectors. CONCLUSIONS: Heterologous prime-boost with ChAd155-hIi-HBV and MVA-HBV, combined with sequential or co-administration of HBc-HBs/AS01B, had an acceptable safety profile, were moderately immunogenic, but no participants showed the expected efficacy outcome.

Humans↗
PubMed2026

Emergence and phylogeography of the dengue vector Aedes aegypti in Southeastern Iran.

BACKGROUND: Aedes (Stegomyia) aegypti (Linnaeus) is the primary vector of dengue, chikungunya, Zika, and yellow fever viruses. Its recent detection in southeastern Iran raises public health concerns about arbovirus spread to new regions. This study provides the first genetic and phylogeographic analysis of Ae. aegypti populations from Sistan and Baluchistan Province (SBP), Iran, to infer their origin and invasion pathways. METHODS: Mitochondrial COI and ND4 genes were analysed in newly collected Ae. aegypti specimens from border areas, ports, and urban centres of SBP. Haplotype network analyses were constructed using the TCS method in PopART, and phylogenetic analyses were conducted using global reference sequences. RESULTS: Iranian specimens comprised 7 COI haplotypes (n = 18) and 10 ND4 haplotypes (n = 17). COI phylogeny placed Iranian specimens into two main clades, while ND4 analysis distributed them across several derived clades, mostly clustering with lineages from Latin America (Brazil, Mexico) or Africa. One Iranian specimen showed a close relationship with a Saudi Arabian sequence (bootstrap: 98%) near the basal region. Combined COI + ND4 analysis revealed a monophyletic clade of Iranian specimens with a Sri Lankan specimen, distinct from other global lineages. The global COI network (n = 47) showed a star-like topology with a dominant haplotype 1 shared among 10 Iranian specimens. The ND4 network (n = 31) revealed a complex topology with 18 haplotypes, where a Saudi Arabian and one Iranian specimen (~30 mutational steps) possibly represented the peripheral root. CONCLUSIONS: Detection of diverse Ae. aegypti clades confirm establishment of this vector in southeastern Iran. Results support multiple introductions and genetic connectivity with Latin America, Africa, and South Asia, pointing to an emerging invasion corridor. Continued genomic surveillance and integrated vector monitoring are urgently needed to guide prevention strategies.

Animals↗
PubMed1979

A longitudinal study of schistosome vector snail populations in Liberia.

Seasonal changes in populations of Biomphalaria pfeifferi and Bulinus globosus were observed at 62 locations in Liberia, West Africa. All varieties of water in both urban and rural locations were sampled. A wet season decrease and dry season increase of B. globosus populations in both urban and rural locations, similar to that reported elsewhere in West Africa, was observed. Similar fluctuations of B. pfeifferi populations were noted. The prevalence of schistosome infected vector snails varied markedly between rural and urban locations. At rural sites parasite prevalence followed the appropriate vector snail prevalence. At urban sites a portion of the vector snail population appeared relatively unaffected by seasonal changes. This stable population harbors a reservoir of infected snails that sustain year round transmission. Human infection was sampled in school children in the study area and prevalence of approximately 50% was found for both Schistosoma mansoni and S. haematobium. Added to the malacologic information this suggests less than hyperendemic transmission. The data suggest that urban environments should receive priorities for control programs.

Animals↗
PubMed1979

Bacteriophage lambda-E. coli K12 vector-host system for gene cloning and expression under lactose promoter control: I. DNA fragment insertion at the lacZ EcoRI restriction site.

Bacteriophage lambda vectors, derived from lambda plac5 were constructed. Their genomes have only one EcoRI restriction site, located near the end of the beta-galactosidase gene. Recombinants, constructed in vitro, having a DNA fragment inserted in the EcoRI site, are lac- and can be easily recognized. Expression of such foreign genes is then under the control of the lac promoter. Mutations Qam73 and Sam7 greatly increase the amount of beta-galactosidase synthesized by the vector bacteriophage. The lambda ZEQS vector has been certified B2 (EK2) by the French control commission "Recombinaisons génétiques in vitro".

Coliphages↗
PubMed1977

The natural decline of Wuchereria bancrofti infection in a vector control situation in the Solomon Islands.

In a situation where filariasis and malaria are transmitted by the same vector, as seen here in the Solomon Islands, the Malaria Eradication Programme aimed at controlling the vector, was found to have an effect on both diseases. In an area of Choiseul island first surveyed by the author in 1970, three follow-up surveys were conducted--in 1974, 1975 and 1976. These showed a progressive decrease in persons infected. When the densities, especially the median microfilarial counts, were expressed as percentage values of the pre-spray survey, there was found to be a proportional decrease over eight years. It is possible that the Anopheline vector needs to be reduced less for the cessation of transmission of filariasis than for malaria. A theoretical ratio was calculated and supporting field evidence presented.

Age Factors↗
PubMed1978

Plasmids useable as gene-cloning vectors in an in vitro packaging by coliphage lambda: "cosmids".

A plasmid which contains a cos site of lambda and can be packaged into lambda bacteriophage particles is termed a "cosmid". Such plasmids can be used as gene cloning vectors in conjunction with an in vitro packaging system. The properties of a new series of cosmids based on the ColE1 replicon are described, including small temperature-sensitive plasmids which have lost mobilisation functions and carry no IS sequences. Amongst these plasmids are vectors for XmaI, BglII, BamHI, HindIII, PstI, KpnI, SalI and EcoRI. It is demonstrated that by using cosmids in particular size ranges these plasmids provide a high efficiency cloning system which yields essentially only hybrid clones without resort to a second selection or screening step, and without prior modification (e.g. phosphatase) treatment of the DNA. Attempts were made to optimise the cloning properties of the cosmid system. An Escherichia coli "gene bank" was obtained with an efficiency of 5 . 10(5) clones per microgram of E. coli DNA, and in which any particular unselected marker may be found in about one out of every 400 clones. It was demonstrated that deletion of mobilisation functions leads to loss of ability to form relaxation-complex without affecting copy number or segregation properties of the temperature-sensitive derivatives. The vectors are amplifiable in chloramphenicol to make up about 50% of the total cellular DNA.

Coliphages↗
PubMed1978

Conjugal transfer of cloning vectors derived from ColE1.

The transfer properties of five cloning vectors derived from ColE1 were studied. Two of the vectors (pSF2124 and pGM706) behaved like wild type ColE1 in that they could be transferred efficiently in the presence of the conjugative plasmid F. The mobilization of the remaining three vectors (pMB9, PBR313 and pBR322) by F was barely detectable. The transfer defect in pBR313 and pBR322 could be complemented by ColK when R64drd11, but not F, was used as the conjugative plasmid. The transferred plasmids could be recovered unchanged from recipients. Conjugal transfer is a potentially useful technique for screening hybrid plasmids in low-risk cloning experiments involving poorly transformable strains.

Conjugation, Genetic↗
PubMed1979

A coliphage lambda vector with enhanced biological containment: lambda gtALO.lambda B.

The biological containment of the lambda gt family of cloning vectors has been enhanced by conditionally blocking DNA replication as well as head and tail morphogenesis. The vector, lambda gtALO.lambda B, was constructed by crossing the Oam29, Aama1 and Lam439 mutations into lambda gt.lambda B. The mutation blocking phage DNA replication, Oam29, is suppressed by suII+ or suIII+. The head gene mutation, Aama1, is suppressed by suIII+ but not by suII+ and the tail gene mutation, Lam439, is suppressed by suII+ but not by suIII+. This allows the option of increasing the biological containment by producing heads when a large amount of cloned DNA is being prepared from an individual isolate. A model recombinant, lambda gt Aama1 Lam439 Oam29.KmR' (lambda gtALO.KmR') was constructed and the containment of the vector was evaluated by the series of standardized experiments required for EK2 certification.

Coliphages↗
PubMed2026

Impact of transfection optimization on adeno-associated virus purification performance and vector quality.

Recombinant adeno-associated virus (rAAV) has shown great promise as a viral vector for gene therapy. However, efficient manufacture of high-quality rAAV to meet clinical demands remains challenging. Here, we optimized rAAV production via a design of experiments (DoE) approach to evaluate the effects of five transfection parameters on vector genome titer, full particle ratio (FE ratio), and viral protein (VP) stoichiometry. The DoE model showed that no single set of transfection conditions could maximize all three responses simultaneously. Subsequently, the materials from DoE-optimized transfections were purified by affinity chromatography followed by anion exchange chromatography (AEX). We observed that AEX recovery declined when capsid loading was high, a situation caused by the combination of high titer with low FE ratio, reducing some of the gains in titer achieved by transfection optimization. Furthermore, AEX had limited capacity to enrich full particles from materials with a very low initial FE ratio. Finally, materials from DoE-optimized transfections showed improved transduction efficiency, which was associated with the ratios of VP1 and VP2 to total VP in the capsid. Overall, this study demonstrates that transfection-derived quality attributes affect purification outcomes and overall vector quality. Our findings highlight the necessity of strategically balancing multiple quality attributes during transfection optimization and provide insights for integrated upstream transfection and downstream purification development.

Adeno-associated virus↗
PubMed2025

Use of an oversized AAV8 vector for CPS1 deficiency results in long-term survival and ammonia control.

Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. There is a high unmet need for an effective therapeutic for this disorder, especially in early neonatal patients where mortality is excessive. However, development of an adeno-associated virus (AAV)-based approach is hampered by large cDNA size and high protein requirement. We developed an oversized AAV vector as a gene therapy to treat CPS1 deficiency. In order to constrain genome size, we utilized small liver-specific promoter/enhancers and a minimal polyadenylation signal. Long-term survival (9 months, end of study) with ammonia control was achieved in AAV8.CPS1-administered Cps1flox/flox mice, while all null vector-injected controls died with marked hyperammonemia; female mice demonstrated improved survival over treated males. While glutamine remained elevated compared to controls, ammonia was controlled in surviving animals. Mice maintained their weights and were not sarcopenic. While drinking water did contain carglumic acid, no nitrogen scavengers were administered. Although there were concerns with vector genomic integrity, these findings demonstrate proof of concept for an oversized gene-therapy approach for a challenging urea-cycle disorder where high-level hepatic protein is essential for survival.

MT: Delivery Strategies↗
PubMed2026

Development of a Recombinant Adeno-Associated Virus Vector for Human T Lymphocyte- and Natural Killer Cell-Targeted Gene Therapy.

Recombinant adeno-associated virus (rAAV) vectors are widely used for gene delivery but show limited efficiency in immune cells, including T lymphocytes and natural killer (NK) cells. To overcome this barrier, we have developed a CD7-targeted rAAV vector (CD7-AAV6/9) featuring a nanobody-fused hybrid capsid derived from a rationally selected chimeric combination of AAV6 and AAV9. CD7-AAV6/9 enables efficient and selective transduction of immortalized and primary human T and NK cells in vitro and in vivo in a humanized mouse model, achieves high production titers, and exhibits markedly reduced off-target transduction compared with wild-type serotypes. Incorporation of a human gene-derived intron into the vector genome to overcome host-mediated transcriptional repression enables robust transgene expression in human CD7+ T lymphocyte and NK cell populations. Together, our findings establish an integrated capsid-genome design framework for targeting human T and NK cells, notoriously challenging immune cell populations for gene therapy, and provide a versatile platform readily adaptable to alternative surface markers and therapeutic payloads.

NK cells↗
PubMed1979

Relative locations among moving spots and visual vector analysis.

How the direction of apparent movement changed with the relative locations among spots was quantitatively measured by the method proposed by Hochberg and Fallon. From the vector-extraction model (proposed by Johansson) expanded as, "The vector to be subtracted depends on the relative location." and the directions of apparent movement, the vector to be subtracted was calculated at each relative location. Consequently data showed (i) the region in which the directions of spots in motion are affected by the frame is finite, and (ii) the degree of the influence is not iniform in the region but is rapidly reduced as spots go away from the frame.

Distance Perception↗
PubMed1975

Theoretical considerations in the vector control of filariasis.

In order to assist in assessing progress of vector control of filariasis a theoretical model is constructed, using retrospective data on infected persons removed to a vector-free situation. This shows that the decrease of microfilaraemia is not regular, but is gradual for the first 3 years and then more rapid, reaching zero at about 10 years. An estimate is made of the level to which the vector must be reduced before transmission of filariasis ceases, showing that the degree of efficiency required is considerably less than for malaria.

Adolescent↗
PubMed2026

Cre-loaded integrase-defective lentiviral vectors for targeted cassette exchange in CHO cells.

Genome-modifying enzymes, such as recombinases and CRISPR-associated nucleases, enable targeted gene insertion when delivered transiently to minimize off-target effects. Precise genome engineering requires controlled enzyme activity, as well as efficient donor DNA transfer. Integrase-defective lentiviral vectors (IDLVs) provide a promising platform for transient episomal DNA transfer; however, their integration efficiency depends on complementary genome-targeting strategies. Here, we engineered Cre-loaded IDLVs (Cre-IDLVs) that co-package lentiviral vector genomes together with bioactive Cre recombinase. Cre was inserted into the Gag region of an integrase-defective gag-pol construct, allowing for efficient encapsidation and protease-mediated release during virion maturation without compromising the viral titer. The resulting particles carried donor cassettes flanked by heterospecific loxP sites. When applied to CHO founder cells harboring compatible genomic loxP landing pads, Cre-IDLVs efficiently mediated recombination-mediated cassette exchange, producing the highest number of G418-resistant colonies among the plasmid ratios tested. Genomic PCR and sequencing confirmed precise locus-specific insertion without detectable random integration in the analyzed clones. These findings establish Cre-IDLVs as a streamlined dual-delivery platform that couples transient recombinase activity with episomal donor DNA transfer. This hybrid lentiviral strategy provides a programmable approach for controlled and site-specific genome modification in mammalian cells.

Integrases↗
PubMed2026

Recent advances for the pharmaceutical production of highly attenuated poxviruses as viral vector platforms.

INTRODUCTION: Highly attenuated poxviruses serve as potent viral vectors, oncolytic agents, and therapeutic vaccines. They can accommodate and stably maintain a large genomic payload of foreign inserts. Their limited replication in human cells provides an excellent safety profile, but it concomitantly necessitates higher doses of infectious particles for full therapeutic efficacy. AREAS COVERED: We review recent advances in bioprocesses for the pharmaceutical production of poxvirus-based vectors, focusing mainly on the vaccinia virus and the Orf virus. These include upstream processing using highly permissive cell substrates, optimized feeding strategies, and a virus phenotype that facilitates downstream processing. The study explores ongoing challenges and identifies strategies to adapt the downstream process to intensified upstream processes in order to achieve an economic end-to-end production. EXPERT OPINION: For notably increased virus yields of up to 2 log after amplification, we propose to replace classic adsorption chromatography by a collective and continuous purification platform for separating the virus from process-related impurities. Filtration operations facilitate process scalability while reducing volumes, which is beneficial for a flow-through polishing to meet pharmaceutical quality attributes. Combined with artificial intelligence modeling, these advancements alleviate financial pressures on healthcare systems and accelerate the production of novel vaccine candidates for clinical use.

Humans↗
PubMedDate not supplied

[Biological control of vectors of human and tropical diseases. Present means and prospects (author's transl)].

Biological control is "direct or indirect use of natural enemies of the injurious species to increase its mortality" (W.H.O., 1963). The more and more frequent apparition of resistant insects populations, the fears as regards the environment, the increase cost of hydrocarbur products and also some technic and operational difficulties to stop transmission by the use of only insecticide pulvérisation, impose this process. Nevertheless, practic use of natural enemies of vectors is yet unusual in spite of important research. (Identification problems, dynamic of species, insufficiency of ethology knowledge particulary of the host specificity, difficulties of application on the vectors which are the most usually widely scattered). For control of insects of medical importance (mosquitoes, black flies, tse-tse flies) it has been used either pathogen agents such as virus bacteria, microsporida or parasit agents such as fungi, mermithid nematods or at last, predators, essentially larvivorus fish. Actually, no biological agent is able to take the place of chemical and physical "traditional" means. In case of mosquito control which is more advanced, the only biological mean which is operational is the use of larvivorus fish and specially Gambusia.

Africa↗