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CLONAL STRAINS OF ATTENUATED VACCINIA VIRUSES AND METHODS OF USE THEREOF RELATED APPLICATIONS Benefit of priority is claimed to U. In particular, provided herein are isolated clonal LIVP strains that have a genome containing a sequence of nucleotides other than a clonal strain whose genome contains the sequence of nucleotides set forth in SEQ ID NO: 10.

SUMMARY Provided are isolated clonal strains from LIVP preparations.

For example, attenuated viruses include recombinant viruses that are modified in one or more viral genes that results in loss or reduced expression of a viral gene or inactivation of a viral protein.

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In some examples, reduced toxicity means that the subject experiences less toxic effects or no toxic effects compared to a subject administered with a virus designated GLV-lh68 having a sequence of nucleotides set forth in SEQ ID NO:9, whereby the virus designated GLV-lh68 is administered in similar amount and under the same dosage regime as the clonal strain.

In other examples, reduced toxicity means that the subject does not die from toxic effects induced upon administration of the virus.

Where permitted, the subject matter of each of the above-referenced applications is incorporated by reference in its entirety.

In some examples, the LIVP clonal strains provided herein have a sequence of nucleotides that has at least 85% sequence identity with the sequence of nucleotides set forth in SEQ ID NO: 10 but does not include the sequence of nucleotides set forth in SEQ ID NO: 10.

Accumulation can be detected by any suitable method, such as imaging the subject to detect virus accumulation, particular in instances in which the virus expresses a detectable protein or a protein that induces a detectable signal or other such marker.

Accumulation also can be detected by sampling body tissues and/or fluids.In some instances the LIVP clonal strain exhibits reduced toxicity and also greater anti-tumor activity, or a combination thereof than the reference LIVP strain, such as the strain with the genome set forth in SEQ ID NO:9, particularly, the strain designated GLV-lh68, also known as GL-ONC1.With any of the provided LIVP clonal strains that exhibit greater anti-tumorigenicity, anti-tumorigenicity can be manifested or assessed in vitro or in vivo upon administration to a subject.The LIVP clonal strains provided herein include any that differs in one or more nucleotides in an open reading frame (ORF) compared to the sequence of nucleotides of the corresponding ORF in the sequence of nucleotides set forth in SEQ ID NO: 10. For example, the difference in one or more nucleotides is one or more nucleotide deletions, substitutions or additions (i.e.insertions), particularly nucleotide changes that change the sequence of the encoded protein.In other examples of the LIVP clonal strains provided herein, an isolated clonal LIVP strain is one that has a genome that does not contain non-viral heterologous nucleic acid that contains an open reading frame encoding a non-viral heterologous protein and exhibits reduced toxicity and/or improved anti- tumorigencity compared to the virus strain designated GLV-lh68 having a sequence of nucleotides set forth in SEQ ID NO:9.

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