Optimization of recombinant adeno-associated viral vectors for human beta-globin gene transfer and transgene expression

Human Gene Therapy
Njeri MainaArun Srivastava

Abstract

Therapeutic levels of expression of the beta-globin gene have been difficult to achieve with conventional retroviral vectors without the inclusion of DNase I-hypersensitive site (HS2, HS3, and HS4) enhancer elements. We generated recombinant adeno-associated viral (AAV) vectors carrying an antisickling human beta-globin gene under the control of either the beta-globin gene promoter/enhancer or the erythroid cell-specific human parvovirus B19 promoter at map unit 6 (B19p6) without any enhancer, and tested their efficacy in a human erythroid cell line (K-562) and in primary murine hematopoietic progenitor cells (c-kit(+)lin()). We report here that (1) self-complementary AAV serotype 2 (scAAV2)-beta-globin vectors containing only the HS2 enhancer are more efficient than single-stranded AAV (ssAAV2)-beta-globin vectors containing the HS2+HS3+HS4 enhancers; (2) scAAV2-beta-globin vectors recombine with scAAV2-HS2+HS3+HS4 vectors after dual-vector transduction, leading to transgene expression; (3) scAAV2-beta-globin as well as scAAV1-beta-globin vectors containing the B19p6 promoter without the HS2 enhancer element are more efficient than their counterparts containing the HS2 enhancer/beta-globin promoter; and (4) scAAV2-B19p6-beta-g...Continue Reading

References

Jan 1, 1992·Current Topics in Microbiology and Immunology·N Muzyczka
Oct 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·C H SrivastavaA Srivastava
Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·D Y TuanD P Lee
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·T R FlotteB J Carter
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·J L MillerA W Nienhuis
Jul 18, 1995·Proceedings of the National Academy of Sciences of the United States of America·M SadelainR C Mulligan
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·P D KesslerB J Byrne
Jan 12, 1999·Nature Medicine·C SummerfordR J Samulski
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·Z YanJ F Engelhardt
Oct 11, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·D DuanJ F Engelhardt
Nov 27, 2001·Science·E Marshall
May 25, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hengjun ChaoChristopher E Walsh
Nov 5, 2002·Methods : a Companion to Methods in Enzymology·Sergei ZolotukhinRichard O Snyder
Jul 23, 2004·Expert Opinion on Biological Therapy·Thomas J Conlon, Terence R Flotte
May 14, 2005·Journal of Virology·Vivian W ChoiDouglas M McCarty
Jun 25, 2005·Current Gene Therapy·Richard O Snyder, Joyce Francis
Jun 28, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Megan GriffeyMark S Sands

❮ Previous
Next ❯

Citations

Mar 15, 2012·Expert Opinion on Biological Therapy·Roberto Gambari
Jan 23, 2013·Translational Research : the Journal of Laboratory and Clinical Medicine·Alisa DongLaura Breda
Apr 14, 2016·Human Gene Therapy·Arun SrivastavaMarina Kleanthous
Jun 21, 2013·Expert Review of Hematology·Laura BredaRoberto Gambari

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.