PLGA-PEG-PLGA thermogel from PolySciTech used in development of gene delivery system to reduce infections during pregnancy

According to the World Health Organization, an estimated 15 million babies are born preterm each year and the complications caused by premature birth are the leading cause of death among children under 5 years of age. One of the causes of premature birth, and other birth complications, is infection of the uterus during pregnancy with bacteria. Naturally occurring antimicrobial peptides in the cervical canal prevent these infections and encouraging the formation of these peptides could potentially protect pregnant women reducing the incidence of premature labor. Recently, researchers at University College London, King’s College London, Great Ormond Street Institute of Child Health (United Kingdom), and University of the Witwatersrand (South Africa) utilized PLGA-PEG-PLGA (PolyVivo AK012) from PolySciTech (www.polyscitech.com) to deliver a viral vector for gene transfer to the cervix in an animal model. They found this could be used to reduce infections during pregnancy. This research holds promise to reduce the incidence of premature birth. Read more: Suff, Natalie, Rajvinder Karda, Juan Antinao Diaz, Joanne Ng, Julien Baruteau, Dany Perocheau, Peter W. Taylor et al. "Cervical gene delivery of the antimicrobial peptide, Human β-defensin (HBD)-3, in a mouse model of ascending infection-related preterm birth." bioRxiv (2019): 643171. https://www.biorxiv.org/content/10.1101/643171v1.abstract

“Approximately 40% of preterm births are preceded by microbial invasion of the intrauterine space: ascent from the vagina is the most common pathway. Within the cervical canal, antimicrobial peptides and proteins (AMPs) help to constitute a barrier which prevents ascending infection. We investigated whether expression of the AMP, human β-defensin-3 (HBD3), in the cervical mucosa prevented bacterial ascent from the vagina into the uterine cavity of pregnant mice. An adeno-associated virus vector containing both the HBD3 gene and GFP transgene (AAV8 HBD3.GFP) or control (AAV8 GFP), was administered intravaginally into E13.5 pregnant mice. Ascending infection was induced at E16.5 using bioluminescent E.coli (E.coli K1 A192PP-lux2). Bioluminescence imaging showed bacterial ascent into the uterine cavity, cellular events that led to premature delivery and a reduction in pups born alive, compared with uninfected controls. In addition, a significant reduction in uterine bioluminescence in the AAV8 HBD3.GFP-treated mice was observed 24 hours post-E.coli infection, compared to AAV8 GFP treated mice, signifying reduced bacterial ascent in AAV8 HBD3.GFP-treated mice. There was also an increase in the number of living pups in AAV HBD3.GFP-treated mice. We propose that HBD3 may be considered a possible candidate for augmenting cervical innate immunity to prevent ascending infection-related preterm birth.”

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