StemCell Therapy

Adenovirus vectors have become a popular delivery platform for gene therapy and vaccines. However, many people have preexisting immunity against adeno-associated viruses (AAVs), which could significantly reduce vector uptake and therefore render the therapeutic cargo they carry ineffective. Even in individuals that lack preexisting immunity, the first inoculation of a vector could induce immune responses that can thwart repeat administration.

To overcome that obstacle, scientists at the University of Pittsburgh created a CRISPR-based system that they say could effectively prevent immunity to the viral vector. The CRISPR tool briefly suppressedgenes that are related to anti-adenovirus antibody production and helped achieve better gene therapy uptake in mice. The results werepublished in Nature Cell Biology.

Samira Kiani, the studys co-senior author, has co-founded SafeGen Therapeutics with the goal to bring this platform to the clinic to enable safer gene therapy.

Accelerate Clinical Operations Across Sponsors, CROs, and Partners

The most advanced life sciences organizations know that digital innovation and multi-platform integrations are essential for enabling product development. New platforms are providing the life sciences industry with an opportunity to improve the efficiency of clinical trials and reduce costs while remaining compliant and reducing risk.

Many clinical trials fail because of the immune response against AAV gene therapy, Kiani said in a statement. And then you cant re-administer the shot because people have developed immunity.

One recent case in point is CanSino Biologics adenovirus type 5 (Ad5)-vectored COVID-19 vaccine. In the shots phase 2 trial, about half of the participants had high levels of preexisting Ad5 neutralizing antibody. These individuals were found to produce significantly lower immune responses to the vaccine than did those with low preexisting anti-Ad5 immunity.

Kiani and colleagues set out to modify the gene expression that's associated with an immune response against AAV, but only temporarilyjust long enough for the therapeutic content to do its jobbecause they didnt want to tamper with normal immune functions.

RELATED:Hopkins team invents non-viral system for getting gene therapy into cells

CRISPR, which can edit out a defective gene or add in a functional one, is already being explored as a gene therapy strategy. So the University of Pittsburgh researchers figured they could hit two birds with one stone by utilizing CRISPR to also control the immune response.

They treated mice with the CRISPR-based system and then re-exposed them to AAV, and the animals didnt make more antibodies against the virus. The treated mice were more receptive to subsequent AAV-delivered gene therapy than were the control animals, the team reported.

Gene therapies hold promise as potential cures to many hard-to-treat diseases that would otherwise require chronic treatment. So scientists have been trying to perfect their transport vehicles for better safety and efficacy.

A team led by scientists at the San Raffaele Telethon Institute for Gene Therapy in Italy, for example,attached the CD47 protein to the surface of lentiviral vectors so they could escape detection and destruction by the immune system. And researchersfrom Johns Hopkins University developed a nonviral delivery system that uses a polymer nano-container, whichreleases the therapy once inside the cell.

Now, Kianihopes to validate the CRISPR-based technology at SafeGen. In addition to its potential as a gene therapy delivery platform, the researchers also found that their method can prevent or treat sepsis in mice, suggesting it might also be useful for treating inflammatory conditions.

Read the original here:
Using CRISPR to improve viral vectors for gene therapy - FierceBiotech

This entry was posted on September 5, 2020 at 1:51 am and is filed under Gene therapy. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |