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Viruses 2012, 4(11), 2806-2830; doi:10.3390/v4112806
Article

Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections

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Received: 3 September 2012; in revised form: 2 October 2012 / Accepted: 2 October 2012 / Published: 6 November 2012
(This article belongs to the Special Issue Advances in Filovirus Research 2012)
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Abstract: There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates.
Keywords: Ebola; Marburg; Phosphorodiamidate Morpholino Oligomer; PMOplus; therapeutic; antiviral Ebola; Marburg; Phosphorodiamidate Morpholino Oligomer; PMOplus; therapeutic; antiviral
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Iversen, P.L.; Warren, T.K.; Wells, J.B.; Garza, N.L.; Mourich, D.V.; Welch, L.S.; Panchal, R.G.; Bavari, S. Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections. Viruses 2012, 4, 2806-2830.

AMA Style

Iversen PL, Warren TK, Wells JB, Garza NL, Mourich DV, Welch LS, Panchal RG, Bavari S. Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections. Viruses. 2012; 4(11):2806-2830.

Chicago/Turabian Style

Iversen, Patrick L.; Warren, Travis K.; Wells, Jay B.; Garza, Nicole L.; Mourich, Dan V.; Welch, Lisa S.; Panchal, Rekha G.; Bavari, Sina. 2012. "Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections." Viruses 4, no. 11: 2806-2830.



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