Methods for modifying the growth rate of a cell
AssigneeRamot at Tel-Aviv University Ltd.
InventorsTamir Tuller, Hadas Zur, Rachel Cohen-Kupiec
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Abstract
Genetically modified cells with at least one codon substituted to a synonymous codon, and with modified replicative fitness as compared to the unmodified cell, wherein a slower translating synonymous codon increases replicative fitness and a faster translating codon decreased replicative fitness are provided. Further, vaccine composition comprising those cells as well as methods for modifying replicative fitness of a cell are provided.
Claims18
A genetically modified cell, comprising at least one endogenous coding sequence comprising a first codon substituted with a synonymous codon, said synonymous codon(s)translating at a different rate than said first codon, wherein said coding sequence comprises a second codon downstream of said synonymous codon(s), wherein said downstream codon translates at a slower rate than the average translational rate of codons 11 to 50 of said coding sequence, and said genetically modified cell comprises a modified free pool of ribosomes that modulates the rate of translation and replicative fitness as compared to a non-genetically modified control cell, and wherein a slower translating synonymous codon increases both said free pool of ribosomes and said replicative fitness of said modified cell and a faster translating synonymous codon decreases both said free pool of ribosomes and said replicative fitness in said genetically modified cell.
A method for modifying replicative fitness in a cell, comprising substituting first codon with a synonymous codon in at least one endogenous coding sequence of said cell, wherein said coding sequence comprises a second codon downstream of said synonymous codon(s), wherein said downstream codon is downstream of codon 50 of said endogenous coding sequence and translates at a slower rate than the average translational rate of codons 11 to 50 of said endogenous coding sequence, and said substituting modifies a free pool of ribosomes that modulate the rate of translation and replicative fitness as compared to a unmodified control cell, and wherein substitution to a slower translating synonymous codon increases both said free pool of ribosomes and said replicative fitness in said modified cell and a substitution to a faster translating synonymous codon decreases both said free pool of ribosomes and said replicative fitness in said modified cell.
Dependencies are inferred from the claim text.