Prashant Mali
University of California, San Diego
82Publications
28H-index
11.3kCitations
Publications 82
Newest
Published on Mar 1, 2019in Nature Methods 26.92
Dhruva Katrekar3
Estimated H-index: 3
(University of California, San Diego),
Genghao Chen1
Estimated H-index: 1
(University of California, San Diego)
+ 5 AuthorsPrashant Mali28
Estimated H-index: 28
(University of California, San Diego)
We present in vivo sequence-specific RNA base editing via adenosine deaminases acting on RNA (ADAR) enzymes with associated ADAR guide RNAs (adRNAs). To achieve this, we systematically engineered adRNAs to harness ADARs, and comprehensively evaluated the specificity and activity of the toolsets in vitro and in vivo via two mouse models of human disease. We anticipate that this platform will enable tunable and reversible engineering of cellular RNAs for diverse applications.
1 Citations Source Cite
Published on Jan 1, 2019in Journal of Molecular Biology 4.89
Kyle Ford1
Estimated H-index: 1
(University of California, San Diego),
Daniella McDonald1
Estimated H-index: 1
(University of California, San Diego),
Prashant Mali28
Estimated H-index: 28
(University of California, San Diego)
Abstract RNA-guided CRISPR (clustered regularly interspaced short palindromic repeat)-associated Cas proteins have recently emerged as versatile tools to investigate and engineer the genome. The programmability of CRISPR–Cas has proven especially useful for probing genomic function in high-throughput. Facile single-guide RNA library synthesis allows CRISPR–Cas screening to rapidly investigate the functional consequences of genomic, transcriptomic, and epigenomic perturbations. Furthermore, by co...
2 Citations Source Cite
Published on Jan 7, 2019in Journal of Visualized Experiments 1.18
Anagha Deshpande3
Estimated H-index: 3
(Discovery Institute),
Bo Rui Chen (Discovery Institute)+ 5 AuthorsAniruddha J. Deshpande1
Estimated H-index: 1
(Discovery Institute)
Gene perturbation studies have been extensively used to investigate the role of individual genes in AML pathogenesis. For achieving complete gene disruption, many of these studies have made use of complex gene knockout models. While these studies with knockout mice offer an elegant and time-tested system for investigating genotype-to-phenotype relationships, a rapid and scalable method for assessing candidate genes that play a role in AML cell proliferation or survival in AML models will help ac...
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Published on Aug 31, 2018in Science 41.06
Reza Kalhor11
Estimated H-index: 11
(Wyss Institute for Biologically Inspired Engineering),
Kian Kalhor2
Estimated H-index: 2
(Sharif University of Technology)
+ 4 AuthorsGeorge M Church G M132
Estimated H-index: 132
(Wyss Institute for Biologically Inspired Engineering)
INTRODUCTION The remarkable development of a single cell, the zygote, into the full organism occurs through a complex series of division and differentiation events that resemble a tree, with the zygote at the base branching through lineages that end in the terminal cell types at the top. Characterizing this tree of development has long been a subject of interest, and the combination of modern genome engineering and sequencing technologies promises a powerful strategy in its service: in vivo barc...
11 Citations Source Cite
Published on Nov 1, 2018in Cell systems 8.98
Udit Parekh2
Estimated H-index: 2
(University of California, San Diego),
Yan Wu1
Estimated H-index: 1
(University of California, San Diego)
+ 4 AuthorsPrashant Mali28
Estimated H-index: 28
(University of California, San Diego)
Summary Understanding the effects of genetic perturbations on the cellular state has been challenging using traditional pooled screens, which typically rely on the delivery of a single perturbation per cell and unidimensional phenotypic readouts. Here, we use barcoded open reading frame overexpression libraries coupled with single-cell RNA sequencing to assay cell state and fitness, a technique we call SEUSS (scalable functional screening by sequencing). Using SEUSS, we perturbed hPSCs with a li...
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Published on Jan 10, 2018in bioRxiv
Ana M. Moreno3
Estimated H-index: 3
(University of California, San Diego),
Nathan D. Palmer1
Estimated H-index: 1
(University of California, San Diego)
+ 5 AuthorsPrashant Mali28
Estimated H-index: 28
(University of California, San Diego)
A major hurdle in protein-based therapeutics is the interaction with the adaptive immune system, which can lead to neutralization by circulating antibodies and clearance of treated cells by cytotoxic T-lymphocytes. One method of circumventing these issues is to use human or humanized proteins which avoid the immune response by self-recognition. However, this approach limits potential protein therapeutics to those of human origin, excluding many exciting effectors and delivery vehicles such as CR...
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Published on Jul 1, 2018in Molecular Therapy 7.01
Ana M. Moreno3
Estimated H-index: 3
(University of California, San Diego),
Xin Fu6
Estimated H-index: 6
(University of California, San Diego)
+ 10 AuthorsPrashant Mali28
Estimated H-index: 28
(University of California, San Diego)
Development of efficacious in vivo delivery platforms for CRISPR-Cas9-based epigenome engineering will be critical to enable the ability to target human diseases without permanent modification of the genome. Toward this, we utilized split-Cas9 systems to develop a modular adeno-associated viral (AAV) vector platform for CRISPR-Cas9 delivery to enable the full spectrum of targeted in situ gene regulation functionalities, demonstrating robust transcriptional repression (up to 80%) and activation (...
4 Citations Source Cite
Published on Jul 1, 2018in Cancer Research 9.13
John Paul Shen10
Estimated H-index: 10
(University of California, San Diego),
Dongxin Zhao2
Estimated H-index: 2
(University of California, San Diego)
+ 9 AuthorsKyle Salinas Sanchez3
Estimated H-index: 3
(University of California, San Diego)
Genetic interactions, in particular negative or "synthetic-lethal" interactions for which simultaneous disruption of two genes causes cell killing, have implications for therapeutic development as has been demonstrated by the clinical success of PARP inhibitors specifically for tumors with loss-of-function mutations in BRCA1/2. However, further applications of synthetic-lethal cancer therapy have been limited by poor understanding of the important genetic interactions in a cancer cell, and how t...
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Published on Mar 12, 2018in bioRxiv
Reza Kalhor11
Estimated H-index: 11
(Harvard University),
Kian Kalhor2
Estimated H-index: 2
(Sharif University of Technology)
+ 3 AuthorsGeorge M Church G M132
Estimated H-index: 132
(Harvard University)
Cellular barcoding using nuclease-induced genetic mutations is an effective approach that is emerging for recording biological information, including developmental lineages. We have previously introduced the homing CRISPR system as a promising methodology for generating such barcodes with scalable diversity and without crosstalk. Here, we present a mouse line (MARC1) with multiple genomically-integrated and heritable homing guide RNAs (hgRNAs). We determine the genomic locations of these hgRNAs,...
2 Citations Source Cite
Published on Dec 1, 2018in Scientific Reports 4.12
Dhruva Katrekar3
Estimated H-index: 3
(University of California, San Diego),
Ana M. Moreno3
Estimated H-index: 3
(University of California, San Diego)
+ 2 AuthorsPrashant Mali28
Estimated H-index: 28
(University of California, San Diego)
Recombinant adeno-associated viruses (AAVs) are among the most commonly used vehicles for in vivo gene delivery. However, their tropism is limited, and additionally their efficacy can be negatively affected by prevalence of neutralizing antibodies in sera. Methodologies to systematically engineer AAV capsid properties would thus be of great relevance. In this regard, we develop here multi-functional AAVs by engineering precision tethering of oligonucleotides onto the AAV surface, and thereby ena...
3 Citations Source Cite
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