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**Cal-1** is an investigational ex vivo anti-HIV gene therapy based on a self-inactivating lentiviral vector, LVsh5/C46. The vector is used to transduce autologous CD4+ T lymphocytes and CD34+ hematopoietic stem/progenitor cells, causing them and their progeny to express a CCR5-directed short hairpin RNA and the membrane-anchored C46 HIV-1 fusion-inhibitory peptide. These complementary mechanisms reduce CCR5 expression and inhibit gp41-mediated viral membrane fusion, thereby making modified cells resistant to HIV-1 entry. Cal-1 was developed by Calimmune and has been evaluated in phase 1/2 studies in HIV-1 infection, including in people with HIV-1-associated high-risk lymphoma undergoing autologous stem cell transplantation. ([pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/26015947/))
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