Lentiviral and Retroviral Vector Systems

2007 ◽  
pp. 39-71 ◽  
Author(s):  
Renata Stripecke ◽  
Noriyuki Kasahara
Keyword(s):  
Retroviral Vector ◽  
Vector Systems

Development of lentiviral vectors for gene therapy for human diseases

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2499-2504 ◽  
Author(s):  
Gary L. Buchschacher ◽  
Flossie Wong-Staal
Keyword(s):  
Gene Therapy ◽  
Human Immunodeficiency Virus ◽  
Retroviral Vectors ◽  
Retroviral Vector ◽  
Vector System ◽  
Human Pathogen ◽  
Vector Systems ◽  
Immunodeficiency Virus ◽  
Clinical Gene Therapy ◽  
Made In

Retroviral vectors derived from murine retroviruses are being used in several clinical gene therapy trials. Recently, progress has been made in the development of vectors based on the lentivirus genus of retroviruses, which ironically includes a major human pathogen, human immunodeficiency virus (HIV). As these vector systems for clinical gene transfer are developed, it is important to understand the rationale behind their design and development. This article reviews the fundamental features of retrovirus replication and of the elements necessary for development of a retroviral vector system, and it discusses why vector systems based on HIV or other lentiviruses have the potential to become important tools in clinical gene therapy.

High Efficiency Gene Transfer to Human Hematopoietic SCID-Repopulating Cells Under Serum-Free Conditions

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3163-3171 ◽  
Author(s):  
Andrea J. Schilz ◽  
Gaby Brouns ◽  
Heike Knöβ ◽  
Oliver G. Ottmann ◽  
Dieter Hoelzer ◽  
...  
Keyword(s):  
Gene Transfer ◽  
High Efficiency ◽  
Marker Gene ◽  
Growth Factor Receptor ◽  
Retroviral Vector ◽  
Scid Mice ◽  
Stable Gene ◽  
Hematopoietic Stem ◽  
Human Cd34 ◽  
Vector Systems

Abstract Stable gene transfer to human pluripotent hematopoietic stem cells (PHSCs) is an attractive strategy for the curative treatment of many genetic hematologic disorders. In clinical trials, the levels of gene transfer to this cell population have generally been low, reflecting deficiencies in both the vector systems and transduction conditions. In this study, we have used a pseudotyped murine retroviral vector to transduce human CD34+ cells purified from bone marrow (BM) and umbilical cord blood (CB) under optimized conditions. After transduction, 71% to 97% of the hematopoietic cells were found to express a low-affinity nerve growth factor receptor (LNGFR) marker gene. Six weeks after transplantation into immunodeficient NOD/LtSz-scid/scid (NOD/SCID) mice, LNGFR expression was detected in 6% to 57% of CD45+ cells in eight of nine engrafted animals. Moreover, proviral DNA was detected in 8.3% to 45% of secondary colonies derived from BM cells of engrafted NOD/SCID mice. Our data show consistent transduction of SCID-repopulating cells (SRCs) and suggest that the efficiency of gene transfer to human hematopoietic repopulating cells can be improved using existing retroviral vector systems and carefully optimized transduction conditions. © 1998 by The American Society of Hematology.

Development of lentiviral vectors for gene therapy for human diseases

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2499-2504 ◽  
Author(s):  
Gary L. Buchschacher ◽  
Flossie Wong-Staal
Keyword(s):  
Gene Therapy ◽  
Human Immunodeficiency Virus ◽  
Retroviral Vectors ◽  
Retroviral Vector ◽  
Vector System ◽  
Human Pathogen ◽  
Vector Systems ◽  
Immunodeficiency Virus ◽  
Clinical Gene Therapy ◽  
Made In

Abstract Retroviral vectors derived from murine retroviruses are being used in several clinical gene therapy trials. Recently, progress has been made in the development of vectors based on the lentivirus genus of retroviruses, which ironically includes a major human pathogen, human immunodeficiency virus (HIV). As these vector systems for clinical gene transfer are developed, it is important to understand the rationale behind their design and development. This article reviews the fundamental features of retrovirus replication and of the elements necessary for development of a retroviral vector system, and it discusses why vector systems based on HIV or other lentiviruses have the potential to become important tools in clinical gene therapy.

High Efficiency Gene Transfer to Human Hematopoietic SCID-Repopulating Cells Under Serum-Free Conditions

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3163-3171 ◽  
Author(s):  
Andrea J. Schilz ◽  
Gaby Brouns ◽  
Heike Knöβ ◽  
Oliver G. Ottmann ◽  
Dieter Hoelzer ◽  
...  
Keyword(s):  
Gene Transfer ◽  
High Efficiency ◽  
Marker Gene ◽  
Growth Factor Receptor ◽  
Retroviral Vector ◽  
Scid Mice ◽  
Stable Gene ◽  
Hematopoietic Stem ◽  
Human Cd34 ◽  
Vector Systems

Stable gene transfer to human pluripotent hematopoietic stem cells (PHSCs) is an attractive strategy for the curative treatment of many genetic hematologic disorders. In clinical trials, the levels of gene transfer to this cell population have generally been low, reflecting deficiencies in both the vector systems and transduction conditions. In this study, we have used a pseudotyped murine retroviral vector to transduce human CD34+ cells purified from bone marrow (BM) and umbilical cord blood (CB) under optimized conditions. After transduction, 71% to 97% of the hematopoietic cells were found to express a low-affinity nerve growth factor receptor (LNGFR) marker gene. Six weeks after transplantation into immunodeficient NOD/LtSz-scid/scid (NOD/SCID) mice, LNGFR expression was detected in 6% to 57% of CD45+ cells in eight of nine engrafted animals. Moreover, proviral DNA was detected in 8.3% to 45% of secondary colonies derived from BM cells of engrafted NOD/SCID mice. Our data show consistent transduction of SCID-repopulating cells (SRCs) and suggest that the efficiency of gene transfer to human hematopoietic repopulating cells can be improved using existing retroviral vector systems and carefully optimized transduction conditions. © 1998 by The American Society of Hematology.

scholarly journals Lentiviral Vectors for Delivery of Gene-Editing Systems Based on CRISPR/Cas: Current State and Perspectives

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1288
Author(s):  
Wendy Dong ◽  
Boris Kantor
Keyword(s):  
Large Scale ◽  
Lentiviral Vector ◽  
Clinical Applications ◽  
Scale Production ◽  
Base Editing ◽  
Epigenome Editing ◽  
Vector Systems ◽  
Dividing Cells

CRISPR/Cas technology has revolutionized the fields of the genome- and epigenome-editing by supplying unparalleled control over genomic sequences and expression. Lentiviral vector (LV) systems are one of the main delivery vehicles for the CRISPR/Cas systems due to (i) its ability to carry bulky and complex transgenes and (ii) sustain robust and long-term expression in a broad range of dividing and non-dividing cells in vitro and in vivo. It is thus reasonable that substantial effort has been allocated towards the development of the improved and optimized LV systems for effective and accurate gene-to-cell transfer of CRISPR/Cas tools. The main effort on that end has been put towards the improvement and optimization of the vector’s expression, development of integrase-deficient lentiviral vector (IDLV), aiming to minimize the risk of oncogenicity, toxicity, and pathogenicity, and enhancing manufacturing protocols for clinical applications required large-scale production. In this review, we will devote attention to (i) the basic biology of lentiviruses, and (ii) recent advances in the development of safer and more efficient CRISPR/Cas vector systems towards their use in preclinical and clinical applications. In addition, we will discuss in detail the recent progress in the repurposing of CRISPR/Cas systems related to base-editing and prime-editing applications.

scholarly journals Jumping Ahead with Sleeping Beauty: Mechanistic Insights into Cut-and-Paste Transposition

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 76
Author(s):  
Matthias T. Ochmann ◽  
Zoltán Ivics
Keyword(s):  
Genetic Engineering ◽  
Structural Data ◽  
Sleeping Beauty ◽  
Preclinical Studies ◽  
Gene Vector ◽  
Functional Information ◽  
Vector Systems ◽  
Novel Variants ◽  
Insight Into ◽  
Cellular Genome

Sleeping Beauty (SB) is a transposon system that has been widely used as a genetic engineering tool. Central to the development of any transposon as a research tool is the ability to integrate a foreign piece of DNA into the cellular genome. Driven by the need for efficient transposon-based gene vector systems, extensive studies have largely elucidated the molecular actors and actions taking place during SB transposition. Close transposon relatives and other recombination enzymes, including retroviral integrases, have served as useful models to infer functional information relevant to SB. Recently obtained structural data on the SB transposase enable a direct insight into the workings of this enzyme. These efforts cumulatively allowed the development of novel variants of SB that offer advanced possibilities for genetic engineering due to their hyperactivity, integration deficiency, or targeting capacity. However, many aspects of the process of transposition remain poorly understood and require further investigation. We anticipate that continued investigations into the structure–function relationships of SB transposition will enable the development of new generations of transposition-based vector systems, thereby facilitating the use of SB in preclinical studies and clinical trials.

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