Biology subjects

Marasco, W. A.

Publications and source records attributed to Marasco, W. A..

2 recordsLinked to original sources

bioRxiv2024

Heritable Immunization Establishes a New Model for Pathogen Control

Heritable immunization represents a promising approach for controlling infectious diseases by embedding immunity directly into the genomes of wild species that spread human pathogens. Here, we report the genetic engineering of Mus musculus to produce a neutralizing, protective single-chain antibody against Borrelia burgdorferi, the causative agent of Lyme disease. Engineered mice stably produced a LA-2 scFv-albumin fusion protein across multiple generations, demonstrating robust heritability and stability of gene expression. Following sequential challenges with infected and uninfected ticks, heterozygous mice exhibited strong resistance to infection, effectively interrupting the Borrelia burgdorferi disease transmission cycle. Having recently established novel protocols to genetically engineer the white-footed mouse, Peromyscus leucopus, a key reservoir of Lyme disease, these findings demonstrate the feasibility of heritable immunization as a potential strategy for mitigating Lyme disease transmission in the environment. More broadly, engineered reservoir immunity may offer a generalizable approach to controlling vector-borne and zoonotic disease with profound potential to improve human health.

bioengineering↗

bioRxiv2020

A novel framework for characterizing genomic haplotype diversity in the human immunoglobulin heavy chain locus

An incomplete ascertainment of genetic variation within the highly polymorphic immunoglobulin heavy chain locus (IGH) has hindered our ability to define genetic factors that influence antibody and B cell mediated processes. To date, methods for locus-wide genotyping of all IGH variant types do not exist. Here, we combine targeted long-read sequencing with a novel bioinformatics tool, IGenotyper, to fully characterize genetic variation within IGH in a haplotype-specific manner. We apply this approach to eight human samples, including a haploid cell line and two mother-father-child trios, and demonstrate the ability to generate high-quality assemblies (>98% complete and >99% accurate), genotypes, and gene annotations, including 2 novel structural variants and 16 novel gene alleles. We show that multiplexing allows for scaling of the approach without impacting data quality, and that our genotype call sets are more accurate than short-read (>35% increase in true positives and >97% decrease in false-positives) and array/imputation-based datasets. This framework establishes a foundation for leveraging IG genomic data to study population-level variation in the antibody response.

genomics↗