Pharmacodynamics of anti-HIV gene therapy using viral vectors and targeted endonucleases.

ABSTRACT:

Objectives

A promising curative approach for HIV is to use designer endonucleases that bind and cleave specific target sequences within latent genomes, resulting in mutations that render the virus replication incompetent. We developed a mathematical model to describe the expression and activity of endonucleases delivered to HIV-infected cells using engineered viral vectors in order to guide dose selection and predict therapeutic outcomes.

Methods

We developed a mechanistic model that predicts the number of transgene copies expressed at a given dose in individual target cells from fluorescence of a reporter gene. We fitted the model to flow cytometry datasets to determine the optimal vector serotype, promoter and dose required to achieve maximum expression.

Results

We

SUBMITTER: Roychoudhury P 

PROVIDER: S-EPMC4954920 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature