New mutant forms of TRIM5α comprising one or more mutations at amino acid positions corresponding to amino acids 324, 328, 330, 333, 335, 336 and/or 337 of wild-type human TRIM5α and which inhibit retrovirus replication are described. These mutants may be used, for example, in gene therapy applications for the prevention and/or treatment of retroviral infection and associated conditions, such as HIV-1 infection and AIDS.