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Kenneth Lundstrom

Publications and source records attributed to Kenneth Lundstrom.

25 records · Page 2Linked to original sources
PubMed2003

Semliki Forest virus vectors for gene therapy.

Semliki Forest virus (SFV) vectors transduce a broad range of mammalian and non-mammalian cells, generating high levels of transient expression of heterologous proteins. Generally, they induce apoptosis in mammalian host cells, leading to rapid cell death. These features have made SFV attractive for various gene therapy applications. Recombinant particles, naked RNA and plasmid DNA containing SFV replicons, demonstrate a strong immune response against recombinantly expressed proteins, which has shown protection against tumour challenges. Intratumoural injection of SFV particles has resulted in tumour regression. SFV vectors have been used for production of retrovirus-like particles. Recently, encapsulation of SFV particles into liposomes has generated highly efficient targeting to tumours. Novel SFV vectors based on point mutations in the non-structural genes, and avirulent SFV strains, have further widened the application range.

Animals↗
PubMed2003

Alphavirus vectors for vaccine production and gene therapy.

Alphavirus vectors demonstrate high expression of heterologous proteins in a broad range of host cells. Replication-deficient as well as replication-competent variants exist. Systemic delivery of many viral antigens has elicited strong antibody responses in immunized mice and primates, and protection against challenges with lethal viruses was obtained. Similarly, prophylactic vaccination was established against tumor challenges. Attention has been paid to the engineering of improved targeting to immunologically active cells, such as dendritic cells. In the area of gene therapy, intratumoral injections of alphavirus vectors have resulted in potentially promising tumor rejection. Moreover, encapsulation of alphavirus particles into liposomes demonstrated efficient tumor targeting in mice with severe combined immunodeficiency, which permitted the initiation of clinical trials for patients with advanced kidney carcinoma and melanoma.

Alphavirus↗
PubMed2002

Alterations in exocytosis induced by neuronal Ca2+ sensor-1 in bovine chromaffin cells.

A variety of Ca2+ binding proteins are known to play an integral role in catecholamine release from synapses as well as secretory cells, such as chromaffin cells. The Drosophila protein frequenin and its mammalian homolog neuronal Ca2+ sensor-1 (NCS-1) belong to a family of Ca2+ sensors with EF hands that bind Ca2+ and then interact with other proteins. Frequenin/NCS-1 has been shown to enhance exocytotic activity in addition to altering Ca2+ channel regulation. To better understand how NCS-1 regulates stimulus-secretion coupling, bovine chromaffin cells were infected with Semliki Forest virus (SFV) vectors containing the rat NCS-1 gene. Cells were studied in the perforated whole-cell patch-clamp configuration. Membrane capacitance was monitored as an indicator of exocytosis-endocytosis. Exocytosis elicited by membrane depolarization was not significantly different between cells infected with SFV expressing green fluorescent protein (GFP) or GFP plus NCS-1, except that the overexpression of NCS-1 resulted in a faster rundown in exocytosis. When cells were stimulated with histamine, NCS-1 overexpression led to higher exocytosis, as well as [Ca2+]i elevation. Immunocytochemistry showed a similar distribution of NCS-1 and phosphatidylinositol 4-kinase beta (PI4Kbeta). NCS-1 and PI4Kbeta coimmunoprecipitate, opening up the possibility that the two proteins directly interact. These results suggest that NCS-1 may regulate cellular activity through the modulation of the phosphatidylinositol signaling pathway.

Action Potentials↗
PubMed2002

Alphavirus vectors as tools in cancer gene therapy.

Alphavirus vectors, particularly those based on the replicon of Semliki Forest virus, have shown great potential as gene delivery vehicles for various applications in cancer gene therapy. The rapid production of high-titer recombinant SFV particles, which show impressive transduction rates in various mammalian cell lines, primary cultures and in vivo, results in high levels of transgene expression. Additionally, SFV vectors induce apoptosis in transduced host cells, which can further increase their efficiency in tumor therapy. Because of the broad host range some attempts to target the gene delivery have been engineered for Sindbis virus vectors, where IgG binding domains of protein A have been introduced into the envelope structure of the recombinant particles to allow attachment of virus to host cells through the interaction of protein A with monoclonal antibodies. SFV vectors have also been employed for the production of retrovirus-like particles for establishment of long-term gene expression. Tumor vaccine approaches have been taken by injection of SFV vectors as naked RNA molecules, DNA plasmids or recombinant particles to achieve both therapeutic and prophylactic efficacy. The continuous improvement of alphavirus vectors will further expand the application range in the future.

Alphavirus↗
PubMed2002

Alphavirus-based vaccines.

Alphavirus vectors can be appliedfor vaccine production as naked RNA molecules, DNA plasmids or recombinant replication-deficient viral particles. The common feature for all these vectors is the alphavirus replicon, which is responsible for the strong RNA amplification in host cells enabling extreme transgene expression levels. Additionally, live replication-proficient virus has elicited reasonable immune responses. For many viral genes, humoral and cellular cytotoxic T-lymphocyte responses have been obtained. In other cases, monoclonal antibodies have been generated against the encoded antigen. Moreover, protection against challenges with lethal doses of virus has been achieved. Alphavirus vaccine applications have been further extended to models for prophylactic tumor therapy.

Alphavirus↗
PubMedDate not supplied

Semliki forest virus-based expression for versatile use in receptor research.

Semliki Forest virus (SFV) vectors have been generated for highly efficient studies on gene expression in a variety of mammalian host cells, including immortalized cell lines as well as primary cells in culture. Moreover, SFV expression has been scaled up for mammalian suspension cultures in spinner flasks and bioreactors for production of large quantities of recombinant proteins for drug screening and purification. The strong preference of expression in neuronal cells in primary cell cultures, in organotypic hippocampal slices and in vivo has made SFV vectors attractive for neurobiological studies. Additionally, the engineering of novel, less cytotoxic and temperature-sensitive SFV mutant vectors has further increased their application range.

Animals↗