High efficiency ex vivo transduction of cells by high titer recombinant retroviral preparations
OwnerDouglas J. Jollyinventor
Life of this patent
Estimating the term…
Abstract
Compositions and methods for the efficient ex vivo introduction of nucleic acid into T cells, non-dividing cells, and cells resistant to standard transduction techniques mediated by high titer recombinant retroviral preparations is described. The recombinant vector constructs carried by the recombinant retrovirus particles code for the production of one or more desired gene products from one or more correponding genes of interest, at least one of the gene products having a therapeutic application. Upon re-introduction into a patient, the transduced cells produce a desired gene product in an amount sufficient to treat a particular disease state.
Claims34
A method of producing transduced mammalian T cells or non-dividing cells, the method comprising:
- (a) obtaining a population of T cells or non-dividing cells from a patient;
- and
- (b) transducing the population of T cells or non-dividing cells ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant retroviral particles carry a vector construct encoding a gene of interest.
A composition comprising an isolated population of mammalian T cells or non-dividing cells, transduced ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant particles carry a vector construct encoding a gene of interest.
A mammalian T cell or non-dividing cell transduced ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant retroviral particles carry a vector construct encoding a gene of interest.
A method of ting a patient having a genetic disease, the method comprising:
- (a) obtaining a population of T cells or non-dividing cells from the patient;
- (b) transducing the population of T cells or non-dividing cells ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant retroviral particles carry a vector construct encoding a gene of interest useful in treating the genetic disease;
- and
- (c) re-introducing into the patient a therapeutically effective amount of the population of transduced T cells or non-dividing cells.
A method of treating a patient having cancer, the method comprising:
- (a) obtaining a population of T cells or non-dividing cells from the patient;
- (b) transducing the population of T cells or non-dividing cells ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant retroviral particles carry a vector construct encoding a gene of interest useful in treating cancer;
- and
- (c) re-introducing into the patient a therapeutically effective amount of the population of transduced T cells or non-dividing cells.
A method of treating a patient having an infectious disease, the method comprising:
- (a) obtaining a population of T cells or non-dividing cells from the patient;
- (b) transducing the population of T cells or non-dividing cells ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant retroviral particles carry a vector construct encoding a gene of interest useful in treating the infectious disease;
- and
- (c) re-introducing into the patient a therapeutically effective amount of the population of transduced T cells or non-dividing cells.
A method of treating a patient having an inflammatory disease, the method comprising:
- (a) obtaining a population of T cells or non-dividing cells from the patient;
- (b) transducing the population of T cells or non-dividing cells ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant retroviral particles carry a vector construct encoding a gene of interest useful in treating the inflammatory disease;
- and
- (c) re-introducing into the patient a therapeutically effective amount of the population of transduced T cells or non-dividing cells.
A method of treating a patient having a degenerative disease, the method comprising:
- (a) obtaining a population of T cells or non-dividing cells from the patient;
- (b) transducing the population of T cells or non-dividing cells ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant retroviral particles carry a vector construct encoding a gene of interest useful in treating the inflammatory disease;
- and
- (c) re-introducing into the patient a therapeutically effective amount of the population of transduced T cells or non-dividing cells.
A method of treating a patient having a cardiovascular disease, the method comprising:
- (a) obtaining a population of T cells or non-dividing cells from the patient;
- (b) transducing the population of T cells or non-dividing cells ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant retroviral particles carry a vector construct encoding a gene of interest useful in treating the cardiovascular disease;
- and
- (c) re-introducing into the patient a therapeutically effective amount of the population of transduced T cells or non-dividing cells.
A method of treating a patient having an autoimmune disease, the method comprising:
- (a) obtaining a population of T cells or non-dividing cells from the patient;
- (b) transducing the population of T cells or non-dividing cells ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant retroviral particles carry a vector construct encoding a gene of interest useful in treating the autoimmune disease;
- and
- (c) re-introducing into the patient a therapeutically effective amount of the population of transduced T cells or non-dividing cells.
A method of modulating the activity of a population of T cells or non-dividing cells in a patient comprising:
- (a) obtaining the population of T cells or non-dividing cells from the patient;
- (b) transducing said population of cells ex vivo with a preparation of high titer recombinant retroviral particles substantially free from contamination with replication competent retrovirus, wherein the recombinant retroviral particles carry a vector construct encoding a protein capable of activating a prodrug;
- (c) re-introducing said population of cells into the patient;
- and
- (c) administering said prodrug to said patient.
Dependencies are inferred from the claim text.