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Drug Delivery pp 143–170Cite as

Viral Vectors for Gene Transfer: Current Status of Gene Therapeutics

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 197))

Abstract

Gene therapy for the correction of inherited or acquired disease has gained increasing importance in recent years. Successful treatment of children suffering from severe combined immunodeficiency (SCID) was achieved using retrovirus vectors for gene transfer. Encouraging improvements of vision were reported in a genetic eye disorder (LCA) leading to early childhood blindness. Adeno-associated virus (AAV) vectors were used for gene transfer in these trials. This chapter gives an overview of the design and delivery of viral vectors for the transport of a therapeutic gene into a target cell or tissue. The construction and production of retrovirus, lentivirus, and AAV vectors are covered. The focus is on production methods suitable for biopharmaceutical upscaling and for downstream processing. Quality control measures and biological safety considerations for the use of vectors in clinical trials are discussed.

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Abbreviations

AAV:

Adeno-associated virus

AAVS1:

Adeno-associated virus integration site 1

Ad:

Adenovirus

ADA:

Adenosine deaminase

cDNA:

Complementary DNA

CMV:

Cytomegalovirus

CNS:

Central nervous system

cPPT:

Central polypurine tract

CsCl:

Caesium chloride

DOC:

Deoxycholate

EIAV:

Equine infectious anemia virus

ELISA:

Enzyme-linked immunosorbent assay

FGFR:

Fibroblast growth factor receptor

GFP:

Green fluorescent protein

GMP:

Good manufacturing practice

HIV:

Human immunodeficiency virus

HSV:

Herpes simplex virus

ITR:

Inverted terminal repeat

lacZ:

β-Galactosidase

LCA:

Leber congenital amaurosis

LMO2:

LIM domain only 2 (rhombotin-like 1)

MoMLV:

Moloney murine leukemia virus

PCR:

Polymerase chain reaction

PIC:

Pre-integration complex

RCV:

Replication-competent virus

RRE:

Rev responsive element

scAAV:

Self-complementary AAV

SCID:

Severe combined immunodeficiency

SDS-PAGE:

SDS polyacrylamide gel electrophoresis

SF9:

Spodoptera frugiperda cell line

SIN:

Self-inactivating

U3 region:

Unique 3′ region

VA-RNA:

Viral associated RNA

VP:

Viral protein

VSV:

Vesicular stomatitis virus

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Authors and Affiliations

  1. Institute of Virology, Charité – Universitätsmedizin Berlin, Hindenburgdamm 27, 12203, Berlin, Germany

    Regine Heilbronn

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  1. Regine Heilbronn
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  2. Stefan Weger
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Correspondence to Regine Heilbronn .

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Editors and Affiliations

  1. FB Biologie, Chemie, Pharmazie, Inst. Pharmazie, FU Berlin, Königin-Luise-Str. 2-4, Berlin, 14195, Berlin, Germany

    Monika Schäfer-Korting

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Heilbronn, R., Weger, S. (2010). Viral Vectors for Gene Transfer: Current Status of Gene Therapeutics. In: Schäfer-Korting, M. (eds) Drug Delivery. Handbook of Experimental Pharmacology, vol 197. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00477-3_5

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