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info@metagenomi.co

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Gene Editing Toolbox

Creating the most diverse genome editing toolbox to address the full spectrum of genetic diseases

Matching the right tool for each therapeutic target

Genet­ic muta­tions are seen in a vari­ety of forms, includ­ing dele­tions, inser­tions, sin­gle base pair changes and sequence repeats across a vari­ety of dif­fer­ent cell types, tis­sues, and organ sys­tems. Addi­tion­al­ly, many dis­eases lack a genet­ic ori­gin but have the poten­tial to be effec­tive­ly and per­ma­nent­ly addressed through genome editing.

At Metageno­mi, we are har­ness­ing the pow­er of metage­nomics to dis­cov­er and devel­op a suite of nov­el edit­ing tools capa­ble of cor­rect­ing any type of genet­ic muta­tion found any­where in the genome. Our com­pre­hen­sive genome edit­ing tool­box includes pro­gram­ma­ble nucle­as­es, base edi­tors, as well as RNA and DNA-medi­at­ed inte­gra­tion sys­tems (includ­ing prime edit­ing sys­tems and CASTs). Giv­en the tar­get­ing den­si­ty of our nucle­ase library, we believe that essen­tial­ly any codon in the human genome could be addressed with our gene edit­ing systems.

Programmable Nucleases

Multiple nucleases to edit any target in the human genome

Our tool­box con­tains thou­sands of CRISPR nucle­as­es allow­ing us to select the ide­al sys­tem for tar­get­ing any giv­en gene in a site-spe­­cif­ic man­ner, poten­tial­ly over­coming a major lim­i­ta­tion of first-gen­er­a­­tion CRISPR sys­tems. In order to mod­i­fy the genome, nucle­as­es are used to cre­ate tar­get­ed genom­ic breaks, trig­gering DNA repair path­ways. This allows us to inte­grate a gene at a tar­get site (knock-in), or deac­ti­vate a gene (knock-down). 

Ultra-Small Systems

Ultra-small nucleases to expand in vivo delivery options

Our ultra-small nucle­as­es are high­ly effi­cient genome edit­ing sys­tems that have the poten­tial for exten­sive ther­a­peu­tic appli­ca­tions. We have pri­or­i­tized find­ing sys­tems to over­come the size con­straints of first gen­er­a­tion nucle­as­es. Our sys­tems are a frac­tion of the size and pack­age eas­i­ly into a sin­gle AAV for tar­get­ing organs beyond what is pos­si­ble with lipid nanopar­ti­cle delivery.

Base Editors

Single nucleotide changes

We lever­age our tool­box of pro­gram­ma­ble nucle­as­es to devel­op a high­ly tar­getable base edit­ing plat­form com­pat­i­ble with a var­iety of deliv­ery tech­nolo­gies. We have dis­cov­ered and engi­neered what we believe to be the small­est CRISPR base edi­tors known. These ultra-small base edi­tors, when deliv­ered in an AAV, could allow us to address neu­ro­mus­cu­lar dis­or­ders in the CNS.

RNA Mediated Integration Systems (RIGS)

Genomic replacements and insertions

Metageno­mi’s RIGS make pro­gram­ma­ble genom­ic mod­i­fi­ca­tions that are encod­ed in RNA tem­plates. Using RIGS we can achieve small edits (prime edit­ing), as well as large edits. Our RIGS plat­form allows us to address more com­plex gene edits such as inser­tions, dele­tions, and all types of point mutations. 

CRISPR Associated Transposases (CASTs)

Large gene integrations

Direct­ed DNA inte­gra­tion has large­ly been con­sid­ered the ulti­mate goal of cor­rec­tive genome edit­ing. This tech­nol­o­gy has the poten­tial to address a large col­lec­tion of com­plex genet­ic dis­eases caused by any loss of func­tion muta­tions, such as cys­tic fibro­sis, where inser­tions of greater than 10,000 bp would be required to address all muta­tions. Our CASTs are being devel­oped to per­form these com­plex gene integrations.

Diverse toolbox

Diverse Tool­box

Our expansive genome editing toolbox enables broad therapeutic applications

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Pre­ci­sion & Efficiency

Our toolbox has the potential to target any codon in the human genome with high precision and efficiency

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Ultra-Small Sys­tems

Our compact systems offer advantages for viral and non-viral in vivo delivery

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Rapid Devel­op­ment

Our highly active natural nucleases and effectors shorten optimization period

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Mod­u­lar Engineering

Chimeras enable access to untargetable sites for precision edits and repairs

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Whol­ly-Owned IP

Diverse enzymes with novel IP and unique characteristics derived from proprietary library

Delivery

Our genome edit­ing tool­box was designed to have broad com­pat­i­bil­i­ty with viral and non­vi­ral deliv­ery technologies

Viral

Non-Viral

We deploy LNP technology for efficient delivery of our gene editing systems to target organs such as the liver in order to address hemophilia, and other metabolic and cardiovascular diseases.

Nonviral

Viral

The ability to package our systems into a single AAV enables us to unlock extrahepatic targets, including those in the CNS and in muscle.

Disease Focus Areas

Strate­gi­cal­ly advanc­ing genet­ic medicines

Ther­a­peu­tic Focus
Liver heart 2

Liv­er and Cardiovascular

Our ini­tial ther­a­peu­tic pro­grams targeting the liver aim to treat dis­eases that have well-defined biol­o­gy, read­i­ly avail­able trans­la­tion­al bio­mark­ers for ear­ly proof-of-con­cept, estab­lished devel­op­ment path­ways based on pri­or drug approvals, and impor­tant unmet med­ical needs. Additionally, we are uti­liz­ing in vivo edit­ing approach­es to tar­get key genes asso­ci­at­ed with major car­dio­vas­cu­lar caus­es of mor­bid­i­ty and mortality.

Cns only

CNS and Muscle

These diseases are caused by diverse mutations that require precision deletions and corrections to address the underlying cause. By optimizing a suite of small, next generation systems we are systematically deploying our toolbox to develop potentially curative therapies for patients with neu­rode­gen­er­a­tive and neu­ro­mus­cu­lar diseases.

Posters & Publications

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