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HIV and Ribozymes

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Gene Therapy for HIV and Chronic Infections

Part of the book series: Advances in Experimental Medicine and Biology ((ASGCT,volume 848))

Abstract

Ribozymes are structured RNA molecules that act as catalysts in different biological reactions. From simple genome cleaving activities in satellite RNAs to more complex functions in cellular protein synthesis and gene regulation, ribozymes play important roles in all forms of life. Several naturally existing ribozymes have been modified for use as therapeutics in different conditions, with HIV-1 infection being one of the most studied. This chapter summarizes data from different preclinical and clinical studies conducted to evaluate the potential of ribozymes to be used in HIV-1 therapies. The different ribozyme motifs that have been modified, as well as their target sites and expression strategies, are described. RNA conjugations used to enhance the antiviral effect of ribozymes are also presented and the results from clinical trials conducted to date are summarized. Studies on anti-HIV-1 ribozymes have provided valuable information on the optimal expression strategies and clinical protocols for RNA gene therapy and remain competitive candidates for future therapy.

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Abbreviations

bRN-P:

Bacterial RNase P

CMV:

Cytomegalovirus

DIS:

Dimerization initiation signal

EGS:

External guide strand

HCV:

Hepatitis C virus

HDV:

Hepatitis delta virus

HH:

Hammerhead

HIV:

Human immunodeficiency virus

Hp:

Hairpin

hRN-P:

Human RNase P

HSC:

Hematopoietic stem cell

LTR:

Long terminal repeat

MMLV:

Moloney murine leukemia virus

MSCV:

Mouse stem cell virus

Pol:

Polymerase

pre:

Precursor

RNase P:

Ribonuclease P

RRE:

Rev response element

Rz(s):

Ribozyme(s)

shRNA:

Short hairpin RNA

SLII:

Stem loop II

snoRNA:

Small nucleolar RNA

snRNA:

Small nuclear RNA

SV40:

Simian virus 40

TAR:

Transactivation response

Tk:

Thymidine kinase

U:

Uridine

UTR:

Untranslated region

VA:

Virus associated

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Acknowledgements

We would like to thank Samantha Burugu and Aïcha Daher (Lady Davis Institute and McGill University) for review of the manuscript. The work done in our laboratory was supported by the Canadian Institutes of Health Research (CIHR) grants [HOP93434 and DCB120266 to A.G.] and by a Banting and Best Canada Graduate Scholarship [CGD-96479 to R.J.S.].

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Authors and Affiliations

  1. Department of Microbiology and Immunology, McGill University, 3999 Cote Ste Catherine Street, Montreal, QC, Canada, H3T 1E2

    Robert J. Scarborough B.Sc. & Anne Gatignol Ph.D.

  2. Lady Davis Institute for Medical Research, 3999 Cote Ste Catherine Street, Montreal, QC, Canada, H3T 1E2

    Robert J. Scarborough B.Sc. & Anne Gatignol Ph.D.

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  1. Robert J. Scarborough B.Sc.
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  2. Anne Gatignol Ph.D.
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Correspondence to Anne Gatignol Ph.D. .

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Editors and Affiliations

  1. University of Amsterdam, Amsterdam, The Netherlands

    Ben Berkhout

  2. The Wistar Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Hildegund C.J. Ertl

  3. University of the Witwatersrand, Johannesburg, South Africa

    Marc S. Weinberg

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Scarborough, R.J., Gatignol, A. (2015). HIV and Ribozymes. In: Berkhout, B., Ertl, H., Weinberg, M. (eds) Gene Therapy for HIV and Chronic Infections. Advances in Experimental Medicine and Biology(), vol 848. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2432-5_5

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