Selection systems for genetically modified cells

A method of providing for selective proliferation, viability or proliferation and viability of a first cell relative to a second cell, comprising:

• introducing a nucleic acid encoding an altered mammalian enzyme into the first cell;
• and
• exposing the first and second cells to conditions that inhibit the unaltered mammalian enzyme but to which the altered mammalian enzyme is resistant;
• whereby the first cell exhibits greater proliferation, viability or proliferation and viability relative to the second cell.

A method of providing for selective proliferation, viability or proliferation and viability of a first cell relative to a second cell, comprising:

• introducing a nucleic acid encoding an altered mammalian enzyme of a nucleotide biosynthesis pathway into the first cell;
• and
• exposing the first and second cells to conditions that inhibit unaltered mammalian enzyme but to which the altered mammalian enzyme is resistant;
• whereby the first cell exhibits greater proliferation, viability or proliferation and viability relative to the second cell.

A method of providing for selective proliferation, viability or proliferation and viability of a first cell relative to a substantially identical or similar type second cell in vivo comprising, introducing a nucleic acid molecule into the first cell;

• and exposing the first and second cells in vivo to conditions that inhibit the proliferation, reduce the viability or inhibit the proliferation and reduce the viability of the substantially identical or similar type second cell, whereby the first cell exhibits greater proliferation, viability or proliferation and viability relative to the second cell,
• wherein:
• the nucleic acid molecule confers resistance to the conditions on the first cell;
• and
• the conditions primarily directly affect only cells similar to the first cell that do not contain the nucleic acid.

A method for transferring a heterologous nucleic acid molecule into an organism, comprising introducing nucleic acids comprising the heterologous nucleic acid molecule and a marker nucleic acid molecule into a first cell;

• introducing the first cell into the organism;
• and exposing the organism to conditions that inhibit the proliferation, reduce viability or inhibit proliferation and reduce viability of a substantially identical or similar type cell that does not contain the marker nucleic acid, wherein:
• the marker nucleic acid molecule confers resistance to the conditions on the first cell;
• and
• the conditions primarily directly affect only cells similar to the first cell that do not contain the marker nucleic acid.

A method of providing a selective advantage for proliferation of a first cell relative to a second cell, comprising introducing a nucleic acid molecule encoding an altered inosine monophosphate dehydrogenase (IMPDH) into the first cell;

• wherein
• the altered IMPDH is resistant to an inhibitor of purine biosynthesis;
• and
• the first cell is a mammalian cell.

A method of providing a selective advantage for proliferation of a first cell relative to a second cell, comprising introducing a nucleic acid molecule encoding an altered dihydroorotate dehydrogenase (DHODH) into the first cell;

• wherein
• the altered DHODH is resistant to an inhibitor of purine biosynthesis;
• and
• the first cell is a mammalian cell.

A method of providing for selective proliferation, viability or proliferation and viability of a first cell relative to a second cell, comprising:

• introducing a nucleic acid encoding a resistant enzyme into the first cell;
• and
• exposing the first and second cells to conditions that inhibit a sensitive form of the enzyme but to which the resistant enzyme is resistant;
• wherein the second cell contains a sensitive form of the enzyme but does not contain the resistant enzyme;
• and
• whereby the first cell exhibits greater proliferation, viability or proliferation and viability relative to the second cell.