Back to results
US 2007/0178066 A1Published application
Pathotropic targeted gene delivery system for cancer and other disorders
OwnerFrederick Hall, John Levy +2inventors
InventorsFrederick Hall, John Levy, Rebecca Reed, Erlinda Gordon
Life of this patent
Estimating the term…
Abstract
Systems for pathotropic (disease-seeking) targeted gene delivery are provided, including viral particles with extremely high titers. In particular, the viral particles are engineered to specifically deliver therapeutic or diagnostic agents to a disease site, such as cancer metastic sites. Personalized dosing regimens are also provided to treat diseases such as cancer efficaciously with reduced adverse side effects.
Claims77
A method of treating a subject having a tumor or tumors containing cancer cells with therapeutic viral particles, the method comprising:
- a) determining the dose of the therapeutic viral particles by
- i) determining the subject's tumor burden as defined by the number of cancer cells residing in the subject's tumor, or the total number of tumor cells in the tumors;
- ii) multiplying the tumor burden by the physiological mulitplicity of infection (pMOI) of the therapeutic viral particles;
- and
- iii) dividing the resultant figure by the titer of the therapeutic viral particles to yield the volume of the therapeutic viral particles to be administered to the subject;
- and
- b) administering the determined dose of the therapeutic viral particles to the subject.
4 more elements
A plasmid comprising:
- e) an optional multiple cloning site functionally-linked to a promoter, wherein the promoter supports expression of a heterologous nucleic acid sequence;
- f) 5′ and 3′ long terminal repeat sequences (LTRs);
- g) a Ψ retroviral packaging sequence;
- h) a CMV promoter positioned upstream of the 5′ LTR sequence;
- i) a nucleic acid sequence operably linked to a promoter, wherein the sequence encodes a polypeptide that confers drug resistance on a producer cell containing the plasmid;
- and
- j) an SV40 origin of replication.
4 more elements
A method for producing a targeted viral vector, the method comprising:
- (a) transiently transfecting a producer cell with:
- i) a first plasmid comprising a nucleic acid sequence encoding the 4070A amphotropic envelope protein modified to contain a collagen binding domain, wherein the nucleic acid sequence is operably linked to a promoter;
- ii) a second plasmid comprising:
- a nucleic acid sequence operably linked to a promoter, wherein the sequence encodes a viral gag-pol polypeptide,
- a nucleic acid sequence operably linked to a promoter, wherein the sequence encodes a polypeptide that confers drug resistance on the producer cell,
- an SV40 origin of replication;
- iii) a third plasmid comprising:
- a heterologous nucleic acid sequence operably linked to a promoter, wherein the sequence encodes a diagnostic or therapeutic polypeptide,
- 5′ and 3′ long terminal repeat sequences (LTRs),
- a Ψ retroviral packaging sequence,
- a CMV promoter upstream of the 5′ LTR,
- a nucleic acid sequence operably linked to a promoter, wherein the sequence encodes a polypeptide that confers drug resistance on the producer cell,
- an SV40 origin of replication,
- wherein the producer cell is a human cell that expresses SV40 large T antigen;
- (b) culturing the producer cells of a) under conditions that allow targeted delivery vector production and release in to the supernatant of the culture;
- (c) isolating and introducing the supernatant in to a closed loop manifold system for collecting the viral particles;
- and
- (d) collecting the targeted delivery vectors.
15 more elements
A kit for the production of targeted viral particles, the kit comprising:
- (a) a container containing a first plasmid comprising a nucleic acid sequence encoding the 4070A amphotropic envelope protein modified to contain a collagen binding domain, wherein the nucleic acid sequence is operably linked to a promoter;
- (b) a container containing a second plasmid comprising:
- a nucleic acid sequence operably linked to a promoter, wherein the sequence encodes a viral gag-pol polypeptide, a nucleic acid sequence operably linked to a promoter, wherein the sequence encodes a polypeptide that confers drug resistance on the producer cell,
- an SV40 origin of replication;
- (c) a container containing a third plasmid comprising:
- a heterologous nucleic acid sequence operably linked to a promoter, wherein the sequence encodes a diagnostic or therapeutic polypeptide,
- 5′ and 3′ long terminal repeat sequences (LTRs),
- a Ψ retroviral packaging sequence,
- a CMV promoter upstream of the 5′ LTR;
- a nucleic acid sequence operably linked to a promoter, wherein the sequence encodes a polypeptide that confers drug resistance on the producer cell,
- an SV40 origin of replication, and
- (d) a container containing a producer cell that expresses SV40 large T antigen;
9 more elements
Dependencies are inferred from the claim text.