Publications

defeatHIV Publications — January 2012 to June 2015


  • Lack of viral control and development of cART escape mutations in macaques after bone marrow transplantation. Peterson CW, Haworth KG, Polacino P, Huang ML, Sykes C, Obenza WM, Repetto AC, Kashuba A, Bumgarner R, De Rosa SC, Woolfrey AE, Jerome KR, Mullins JI, Hu SL, Kiem HP. AIDS Journal, in press, 2015. [PMCID:  In Process].
  • Lentivirus-mediated gene transfer in hematopoietic stem cells is impaired in SHIV-infected, ART-treated nonhuman primates.  Younan PM, Peterson CW, Polacino P, Kowalski JP, Obenza W, Miller HW, Milless BP, Gafken P, DeRosa SC, Hu SL, Kiem HP.  Mol Ther,23(5) 943-951. 2015 May; PMID: 25648264; PMCID: PMC4427875
  • Assembly and characterization of megaTALs for hyperspecific genome engineering applications. Boissel S, Scharenberg AM. Methods Mol Biol. 2015;1239:171-96. doi: 10.1007/978-1-4939-1862-1_9.  PMID: 25408406.
  • Cell-specific RNA aptamer against human CCR5 Specifically Targets HIV-1 Infectivity. Zhou J, Satheesan S, Li H, Weinberg M, Morris K, Burnett J, and Rossi JJ. Chem & Biol J. 2015. 22(3):379-90. PMID: 25754473; PMCID: PMC4369413.


  • AAV-mediated delivery of zinc finger nucleases targeting hepatitis B virus inhibits active replication. Weber ND, Stone D, Sedlak RH, De Silva Feelixge HS, Roychoudhury P, Schiffer JT, Aubert M, Jerome KR. PLoS One. 2014 May 14;9(5):e97579. PMID: 24827459; PMCID: PMC4020843.
  • The potential advantages of digital PCR for clinical virology diagnostics. Hall Sedlak R, Jerome KR. Expert Rev Mol Diagn. 2014 May;14(4):501-7. PMID: 24724628.
  • HIV eradication–from Berlin to Boston. Cannon PM, Kohn DB, Kiem HP. Nat Biotechnol. 2014 Apr;32(4):315-6. PMID: 24714473.
  • DNA cleavage enzymes for treatment of persistent viral infections: Recent advances and the pathway forward. Weber ND, Aubert M, Dang CH, Stone D, and Jerome KR. Virology. 2014 Apr;454-455:353-61. PMID: 24485787; PMCID: PMC3988252.
  • The majority of CD4+ T-cell depletion during acute SHIV89.6P infection occurs in uninfected cells. Matrajt L, Younan PM, Kiem HP, and Schiffer JT. J Virol. 2014 Mar;88(6):3202-12. PMID: 24390339; PMCID: PMC3957925.
  • Genetically Modified Hematopoietic Stem Cell Transplantation for HIV-1 Infected Patients: Can we achieve a Cure? Younan P, Kowalski J, and Kiem HP. Mol Ther. 2014 Feb;22(2):257-64. PMID: 24220323; PMCID: PMC3916050.
  • megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering. Boissel S, Jarjour J, Astrakhan A, Adey A, Gouble A, Duchateau P, Shendure J, Stoddard BL, Certo MT, Baker D, and Scharenberg AM. Nucleic Acids Res. 2014 Feb;42(4):2591-601. PMID: 24285304; PMCID: PMC3936731.
  • In vitro Inactivation of Latent HSV by Targeted Mutagenesis Using an HSV-specific Homing Endonuclease. Aubert M, Boyle NM, Stone D, Stensland L, Huang ML, Magaret AS, Galetto R, Rawlings DJ, Scharenberg AM, and Jerome KR. Mol Ther Nucleic Acids. 2014 Feb 4;3e146. PMID: 24496438; PMCID: PMC3951911.
  • Novel fluorescent genome editing reporters for monitoring DNA repair pathway utilization at endonuclease-induced breaks. Kuhar R, Gwiazda KS, Humbert O, Mandt T, Pangallo J, Brault M, Khan I, Maizels N, Rawlings DJ, Scharenberg AM, and Certo MT. Nucleic Acids Res. 2014 Jan; 42(1): e4. PMID: 24121685; PMCID: PMC3874187.
  • Engineering and flow-cytometric analysis of chimeric LAGLIDADG homing endonucleases from homologous I-OnuI-family enzymes. Baxter SK, Scharenberg AM, Lambert AR. Methods Mol Biol. 2014;1123:191-221. PMID: 24510269; PMCID: PMC4134777.
  • Cell-type specific, aptamer-functionalized agents for targeted disease therapy. Zhou J and Rossi, JJ. Mol Ther Nucl Acid. 2014 3:e169. PMID: 24936916; PMCID: PMC4078761.
  • Homing endonuclease target determination using SELEX adapted for yeast surface display. Jacoby K, Scharenberg AM. Methods Mol Biol. 2014;1123:165-90. PMID: 24510268.


  • Genetic modification of hematopoietic stem cells as a therapy for HIV/AIDS. Younan P, Kowalski J, and Kiem HP. Viruses. 2013 Dec; 5(12): 2946-62. PMID: 24287598; PMCID: PMC3967155.
  • Development of hematopoietic stem cell based gene therapy for HIV-1 infection: considerations for proof of concept studies and translation to standard medical practice. DiGiusto DL, Stan R, Krishnan A, Li H, Rossi JJ, and Zaia JA. Viruses. 2013 Nov; 5(11): 2898-919. PMID: 24284880; PMCID: PMC3856421.
  • Tolerance of droplet-digital PCR vs real-time quantitative PCR to inhibitory substances. Dingle TC, Sedlak RH, Cook L, and Jerome KR. Clin Chem. 2013 Nov; 59(11): 1670-2. PMID: 24003063; PMCID: PMC4247175.
  • Robust suppression of env-SHIV viremia in Macaca nemestrina by 3-drug ART is independent of timing of initiation during chronic infection. Peterson CW, Younan P, Polacino PS, Maurice NJ, Miller HW, Prlic M, Jerome KR, Woolfrey AE, Hu SL, and Kiem HP. Journal of medical primatology. 2013 Oct; 42(5): 237-46. PMID: 24025078; PMCID: PMC3772551.
  • Positive selection of mC46-expressing CD4+ T cells and maintenance of virus specific immunity in a primate AIDS model. Younan PM, Polacino P, Kowalski JP, Peterson CW, Maurice NJ, Williams NP, Ho O, Trobridge GD, Von Laer D, Prlic M, Beard BC, DeRosa S, Hu SL, and Kiem HP. Blood. 2013 Jul 11; 122(2): 179-87. PMID: 23719296; PMCID: PMC3709653.
  • Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART. Peterson CW, Younan P, Jerome KR, and Kiem HP. Gene therapy. 2013 Jul;20(7):695-702. PMID: 23364313; PMCID: PMC3725618.
  • Predictors of hepatitis B cure using gene therapy to deliver DNA cleavage enzymes: a mathematical modeling approach. Schiffer JT, Swan DA, Stone D, and Jerome KR. PLoS computational biology. 2013 Jul; 9(7): e1003131. PMID: 23861664; PMCID: PMC3701691.
  • Targeted gene disruption to cure HIV. Stone D, Kiem HP, and Jerome KR. Current opinion in HIV and AIDS. 2013 May; 8(3): 217-23. PMID: 23478911; PMCID: PMC4226633.
  • Combinatorial RNA-based gene therapy for the treatment of HIV/AIDS. Chung J, DiGiusto DL, and Rossi JJ. Expert opinion on biological therapy. 2013 Mar; 13(3): 437-45. PMID: 23394377; PMCID: PMC3732042.
  • Viral diagnostics in the era of digital polymerase chain reaction. Sedlak RH and Jerome KR. Diagnostic microbiology and infectious disease. 2013 Jan; 75(1): 1-4. PMID: 23182074; PMCID: PMC3519953.
  • Aptamer-based therapeutics: new approaches to combat human viral diseases. Shum KT, Zhou J, and Rossi JJ. Pharmaceuticals. 2013 6(12): 1507-42. PMID: 24287493; PMCID: PMC3873675.
  • Functional in vivo delivery of multiplexed anti-HIV-1 siRNAs via a chemically synthesized aptamer with a sticky bridge. Zhou J, Neff CP, Swiderski P, Li H, Smith DD, Aboellail T, Remling-Mulder L, Akkina R, Rossi JJ. Molecular Therapy. 2013 21(1), 192-200. PMID: 23164935; PMCID: PMC3538316.


  • Efficient generation, purification, and expansion of CD34(+) hematopoietic progenitor cells from nonhuman primate-induced pluripotent stem cells. Gori JL, Chandrasekaran D, Kowalski JP, Adair JE, Beard BC, D’Souza SL, and Kiem HP. Blood. 2012 Sep 27; 120(13): e35-44. PMID: 22898598; PMCID: PMC3460690.
  • Coupling endonucleases with DNA end-processing enzymes to drive gene disruption. Certo MT, Gwiazda KS, Kuhar R, Sather B, Curinga G, Mandt T, Brault M, Lambert AR, Baxter SK, Jacoby K, Ryu BY, Kiem HP, Gouble A, Paques F, Rawlings DJ, and Scharenberg AM. Nat Methods. 2012 Sep 2. PMID: 22941364; PMCID: PMC3602999.
  • Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases. Baxter S, Lambert AR, Kuhar R, Jarjour J, Kulshina N, Parmeggiani F, Danaher P, Gano J, Baker D, Stoddard BL, and Scharenberg AM. Nucleic Acids Res. 2012 Sep; 40(16): 7985-8000. PMID: 22684507; PMCID: PMC3439895.
  • Targeted DNA mutagenesis for the cure of chronic viral infections. Schiffer JT, Aubert M, Weber ND, Mintzer E, Stone D, and Jerome KR. J Virol. 2012 Sep; 86(17): 8920-36. PMID: 22718830; PMCID: PMC3416169.
  • Current translational and clinical practices in hematopoietic cell and gene therapy. Digiusto DL and Kiem HP. Cytotherapy. 2012 Aug; 14(7): 775-90. PMID: 22799276; PMCID: PMC3655758.
  • Hematopoietic-stem-cell-based gene therapy for HIV disease. Kiem HP, Jerome KR, Deeks SG, and McCune JM. Cell Stem Cell. 2012 Feb 3; 10(2): 137-47. PMID: 22305563; PMCID: PMC3274769.

Featured Article from the Literature

Evidence for the Cure of HIV Infection by CCR5∆32/∆32 Stem Cell Transplantation
Allers et al, Blood. 2011 Mar 10;117(10):2791-9. Epub 2010 Dec 8.

Abstract
HIV entry into CD4(+) cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5Δ32/Δ32 stem cells. However, it was expected that the long-lived viral reservoir would lead to HIV rebound and disease progression during the process of immune reconstitution. In the present study, we demonstrate successful reconstitution of CD4(+) T cells at the systemic level as well as in the gut mucosal immune system after CCR5Δ32/Δ32 stem cell transplantation, while the patient remains without any sign of HIV infection. This was observed although recovered CD4(+) T cells contain a high proportion of activated memory CD4(+) T cells, ie, the preferential targets of HIV, and are susceptible to productive infection with CXCR4-tropic HIV. Furthermore, during the process of immune reconstitution, we found evidence for the replacement of long-lived host tissue cells with donor-derived cells, indicating that the size of the viral reservoir has been reduced over time. In conclusion, our results strongly suggest that cure of HIV has been achieved in this patient.
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Publications from Our Collaboratory

2013

2012

2011 – earlier